Alzheimer disease

Summary

Alzheimer disease (MONDO:0004975) is a disease (an umbrella term covering 5 Mondo subtypes) with 74 cohort genes (6,214 GWAS associations across 235 studies) and 3,050 clinical trials. The dominant Reactome pathway is Defective B3GALTL causes PpS (6 cohort genes). Top therapeutic interventions include donepezil, rivastigmine, and memantine.

At a glance

• Umbrella term: 5 Mondo subtypes
• Cohort genes: 74
• GWAS associations: 6,214
• ClinVar variants: 447
• Clinical trials: 3,050

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Alzheimer disease
Mondo ID	MONDO:0004975
MeSH	D000544
Orphanet	238616
DOID	DOID:10652
ICD-10-CM	G30
ICD-11	1611724421
NCIT	C2866
SNOMED CT	142811000119104
UMLS	C0002395
MedGen	1853
Is cancer (heuristic)	no

Also known as: AD · Alzheimer dementia · Alzheimer disease · Alzheimer disease, familial · Alzheimer’s dementia · Alzheimer’s disease · Alzheimers disease · presenile and senile dementia

Data availability: 447 ClinVar variants · 6,214 GWAS associations (235 studies) · 2 GenCC gene-disease records · 1 HPO phenotype · 517 cell lines.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › cognitive disorder › dementia › Alzheimer disease

Related subtypes (8): vascular dementia, Lewy body dementia, hereditary dementia, dementia pugilistica, parkinsonism with dementia of Guadeloupe, AIDS dementia complex, progressive dementia with neuroserpin inclusion bodies, childhood-onset dementia

Subtypes (5): Alzheimer disease 16, Alzheimer disease 17, Alzheimer disease 18, Alzheimer disease 19, familial Alzheimer disease

Genetics & variants

GWAS landscape

6,214 GWAS associations across 235 studies. Top hits map to 18 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs429358	2e-303	APOE	?	3.21
rs2075650	1e-295	TOMM40	G	2.53
rs41289512	6e-276	NECTIN2	G	35.5
rs1081105	1e-231	APOE - APOC1	C	32.5
rs157580	8e-220	TOMM40	G	31.65
rs3925681	7e-162	APOC1	?
rs6859	1e-155	NECTIN2	?
rs4420638	8e-149	APOC1	?	3.45
rs28399637	2e-143	BCAM	A	25.51
rs2927468	4e-108	NECTIN2	?
rs7412	1e-99	APOE	T	21.2
rs157595	1e-97	APOC1 - APOC1P1	?
rs261291	4e-84	ALDH1A2	?
rs769449	2e-83	APOE	?	3.87
rs56131196	6e-77	APOC1	?	3.26
rs77301115	7e-74	TOMM40	?
rs60049679	2e-70	APOC1P1, APOC1P1	?
rs71352238	7e-69	TOMM40	?	3.18
rs138607350	3e-65	NECTIN2	G	17.06
rs79701229	1e-64	NECTIN2	A	16.99
rs6733839	2e-64	BIN1 - NIFKP9	?	1.15
rs157582	4e-63	TOMM40	?	2.73
rs61812598	6e-63	IL6R	G
rs483082	1e-62	APOE - APOC1	?	2.64
rs10407439	1e-58	BCAM - NECTIN2	A	16.14
rs449647	2e-58	APOE	?
rs2965169	3e-57	BCL3	C	15.94
rs58826447	7e-54	BCAM - NECTIN2	?
rs406315	5e-50	NECTIN2	?
rs116949436	7e-50	CLPTM1	A	14.85

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST002245	Lambert JC	2013	17,008	37,154	Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease.
GCST001026	Naj AC	2011	8,309	7,366	Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease.
GCST001025	Hollingworth P	2011	6,688	13,685	Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease.
GCST000479	Harold D	2009	3,941	7,848	Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease.
GCST001743	Jonsson T	2012	3,550	8,888	Variant of TREM2 associated with the risk of Alzheimer’s disease.
GCST002422	Perez-Palma E	2014	2,540	2,029	Overrepresentation of glutamate signaling in Alzheimer’s disease: network-based pathway enrichment using meta-analysis of genome-wide association studies.
GCST002462	Gusareva ES	2014	2,259	6,017	Genome-wide association interaction analysis for Alzheimer’s disease.
GCST000480	Lambert JC	2009	2,032	5,328	Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease.
GCST001449	Lambert JC	2012	2,025	5,328	Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer’s disease.
GCST001963	Reitz C	2013	1,968	3,928	Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ϵ4,and the risk of late-onset Alzheimer disease in African Americans.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	3
Tier 2: splice/UTR	1
Tier 3: regulatory	4
Tier 4: intronic/intergenic	42

MAF distribution

Bucket	Variants
common (>=0.05)	43
low_freq (0.01-0.05)	4
rare (<0.01)	1
unknown	2

Functional consequences

Consequence	Count
intron_variant	26
intergenic_variant	12
non_coding_transcript_exon_variant	4
regulatory_region_variant	4
missense_variant	3
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs429358	19	44908684	T>C	0.05	missense_variant	APOE	2e-303	Tier 1: coding
rs2075650	19	44892362	A>C,G	0.14	intron_variant	TOMM40	1e-295	Tier 4: intronic/intergenic
rs41289512	19	44848259	C>G	0.039	intron_variant	NECTIN2	6e-276	Tier 4: intronic/intergenic
rs1081105	19	44909698	A>C,G	0.028	non_coding_transcript_exon_variant	APOE - APOC1	1e-231	Tier 4: intronic/intergenic
rs157580	19	44892009	G>A,C,T	0.395	intron_variant	TOMM40	8e-220	Tier 4: intronic/intergenic
rs3925681	19	44917843	G>A	0.05	intron_variant	APOC1	7e-162	Tier 4: intronic/intergenic
rs6859	19	44878777	A>G,T	0.05	3_prime_UTR_variant	NECTIN2	1e-155	Tier 2: splice/UTR
rs4420638	19	44919689	A>G	0.05	intergenic_variant	APOC1	8e-149	Tier 4: intronic/intergenic
rs28399637	19	44820881	G>A	0.316	intron_variant	BCAM	2e-143	Tier 4: intronic/intergenic
rs2927468	19	44854682	A>G	0.05	intron_variant	NECTIN2	4e-108	Tier 4: intronic/intergenic
rs7412	19	44908822	C>T	0.08	missense_variant	APOE	1e-99	Tier 1: coding
rs157595	19	44922203	A>G,T	0.05	intergenic_variant	APOC1 - APOC1P1	1e-97	Tier 4: intronic/intergenic
rs261291	15	58387979	T>A,C	0.05	intergenic_variant	ALDH1A2	4e-84	Tier 4: intronic/intergenic
rs769449	19	44906745	G>A	0.05	intron_variant	APOE	2e-83	Tier 4: intronic/intergenic
rs56131196	19	44919589	G>A	0.05	intergenic_variant	APOC1	6e-77	Tier 4: intronic/intergenic
rs77301115	19	44893716	G>A	0.05	intron_variant	TOMM40	7e-74	Tier 4: intronic/intergenic
rs60049679	19	44926451	G>A,C,T	0.05	intron_variant	APOC1P1, APOC1P1	2e-70	Tier 4: intronic/intergenic
rs71352238	19	44891079	T>C	0.05	regulatory_region_variant	TOMM40	7e-69	Tier 3: regulatory
rs138607350	19	44860563	T>G	0.006	intron_variant	NECTIN2	3e-65	Tier 4: intronic/intergenic
rs79701229	19	44881674	G>A	0.013	intron_variant	NECTIN2	1e-64	Tier 4: intronic/intergenic
rs6733839	2	127135234	C>G,T	0.05	intron_variant	BIN1 - NIFKP9	2e-64	Tier 4: intronic/intergenic
rs157582	19	44892962	C>A,G,T	0.05	intron_variant	TOMM40	4e-63	Tier 4: intronic/intergenic
rs61812598	1	154447611	G>A	0.05	intron_variant	IL6R	6e-63	Tier 4: intronic/intergenic
rs483082	19	44912921	G>T	0.262	non_coding_transcript_exon_variant	APOE - APOC1	1e-62	Tier 4: intronic/intergenic
rs10407439	19	44838691	A>G,T	0.296	intergenic_variant	BCAM - NECTIN2	1e-58	Tier 4: intronic/intergenic
rs449647	19	44905307	A>G,T	0.05	regulatory_region_variant	APOE	2e-58	Tier 3: regulatory
rs2965169	19	44747899	A>C	0.388	non_coding_transcript_exon_variant	BCL3	3e-57	Tier 4: intronic/intergenic
rs58826447	19	44825122	T>A,G	0.05	intergenic_variant	BCAM - NECTIN2	7e-54	Tier 4: intronic/intergenic
rs406315	19	44880859	G>A,C	0.05	intron_variant	NECTIN2	5e-50	Tier 4: intronic/intergenic
rs116949436	19	44960129	G>A	0.011	intron_variant	CLPTM1	7e-50	Tier 4: intronic/intergenic

ClinVar germline variants

447 retrieved; paginated sample, class counts are floors:

181 uncertain significance, 153 likely benign, 36 conflicting classifications of pathogenicity, 22 benign/likely benign, 21 benign, 18 pathogenic, 12 likely pathogenic, 2 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity; other, 1 conflicting classifications of pathogenicity; other; risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
1353302	NC_000021.8:g.(?27251861)(27544138_?)dup	APP	Pathogenic	criteria provided, single submitter
1457308	NM_000484.4(APP):c.2145_2146delinsTG (p.Ile716Val)	APP	Pathogenic	criteria provided, multiple submitters, no conflicts
18087	NM_000484.4(APP):c.2077G>C (p.Glu693Gln)	APP	Pathogenic	criteria provided, multiple submitters, no conflicts
18088	NM_000484.4(APP):c.2149G>A (p.Val717Ile)	APP	Pathogenic	criteria provided, multiple submitters, no conflicts
18089	NM_000484.4(APP):c.2149G>T (p.Val717Phe)	APP	Pathogenic	criteria provided, multiple submitters, no conflicts
18091	NM_000484.4(APP):c.2075C>G (p.Ala692Gly)	APP	Pathogenic	no assertion criteria provided
18093	NM_000484.4(APP):c.2010_2011inv (p.Lys670_Met671delinsAsnLeu)	APP	Pathogenic	criteria provided, multiple submitters, no conflicts
18097	NM_000484.4(APP):c.2143G>A (p.Val715Met)	APP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
18098	NM_000484.4(APP):c.2078A>G (p.Glu693Gly)	APP	Pathogenic	no assertion criteria provided
18099	NM_000484.4(APP):c.2077G>A (p.Glu693Lys)	APP	Pathogenic	criteria provided, single submitter
18100	NM_000484.4(APP):c.2141C>T (p.Thr714Ile)	APP	Pathogenic	criteria provided, single submitter
18101	NM_000484.4(APP):c.2080G>A (p.Asp694Asn)	APP	Pathogenic	criteria provided, multiple submitters, no conflicts
18102	NM_000484.4(APP):c.2140A>G (p.Thr714Ala)	APP	Pathogenic	criteria provided, multiple submitters, no conflicts
18106	NM_000484.4(APP):c.2018C>T (p.Ala673Val)	APP	Pathogenic	no assertion criteria provided
2423147	NC_000021.8:g.(?27113910)(27542938_?)dup	APP	Pathogenic	criteria provided, single submitter
2498894	NM_000484.4(APP):c.2146A>T (p.Ile716Phe)	APP	Pathogenic	criteria provided, multiple submitters, no conflicts
98240	NM_000484.4(APP):c.2147T>C (p.Ile716Thr)	APP	Pathogenic	criteria provided, single submitter
127268	NC_000021.7:g.13636378_28138533dup	CYYR1	Pathogenic	no assertion criteria provided
1184625	Single allele	GABPA	Pathogenic	criteria provided, single submitter
599622	NM_000021.4(PSEN1):c.869-1G>A	PSEN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
18094	NM_000484.4(APP):c.2137G>A (p.Ala713Thr)	APP	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3690355	NM_000484.4(APP):c.2138C>A (p.Ala713Glu)	APP	Likely pathogenic	criteria provided, single submitter
599607	NM_001288705.3(CSF1R):c.2671G>C (p.Ala891Pro)	CSF1R	Likely pathogenic	criteria provided, single submitter
599608	NM_001288705.3(CSF1R):c.2326C>T (p.His776Tyr)	CSF1R	Likely pathogenic	criteria provided, single submitter
599611	NM_002087.4(GRN):c.264+1G>A	GRN	Likely pathogenic	criteria provided, multiple submitters, no conflicts
599620	NM_001377265.1(MAPT):c.2260C>T (p.His754Tyr)	MAPT	Likely pathogenic	criteria provided, single submitter
4682122	NM_000021.4(PSEN1):c.314T>C (p.Phe105Ser)	PSEN1	Likely pathogenic	criteria provided, single submitter
599623	NM_000021.4(PSEN1):c.665A>C (p.Gln222Pro)	PSEN1	Likely pathogenic	criteria provided, single submitter
599624	NM_000021.4(PSEN1):c.510_511insTAT (p.Ser170_Leu171insTyr)	PSEN1	Likely pathogenic	criteria provided, single submitter
599625	NM_000021.4(PSEN1):c.1297C>T (p.Pro433Ser)	PSEN1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 63 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 6

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
CLU	CLU	GWAS
APOE	APOE	GWAS, Orphanet
APP	APP	GWAS, Orphanet
MAPT	MAPT	GWAS, Orphanet
PCDH11X	PCDH11X	GWAS
SORL1	SORL1	GWAS, Orphanet

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ECE2	Limited	Autosomal dominant	Alzheimer disease

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
APOE	Orphanet:329481	Lipoprotein glomerulopathy
APOE	Orphanet:412	Dysbetalipoproteinemia
APP	Orphanet:100006	ABeta amyloidosis, Dutch type
APP	Orphanet:1020	Early-onset autosomal dominant Alzheimer disease
APP	Orphanet:324703	ABetaL34V amyloidosis
APP	Orphanet:324708	ABeta amyloidosis, Iowa type
APP	Orphanet:324713	ABeta amyloidosis, Italian type
APP	Orphanet:324718	ABetaA21G amyloidosis
APP	Orphanet:324723	ABeta amyloidosis, Arctic type
MAPT	Orphanet:100069	Semantic dementia
MAPT	Orphanet:100070	Progressive non-fluent aphasia
MAPT	Orphanet:240071	Classic progressive supranuclear palsy syndrome
MAPT	Orphanet:240085	Progressive supranuclear palsy-predominant parkinsonism syndrome
MAPT	Orphanet:240094	Progressive supranuclear palsy-pure akinesia with gait freezing syndrome
MAPT	Orphanet:240103	Progressive supranuclear palsy-corticobasal syndrome
MAPT	Orphanet:240112	Progressive supranuclear palsy-progressive non-fluent aphasia syndrome
MAPT	Orphanet:275864	Behavioral variant of frontotemporal dementia
RORA	Orphanet:528084	Non-specific syndromic intellectual disability
RTN2	Orphanet:100993	Autosomal dominant spastic paraplegia type 12
BIN1	Orphanet:169186	Autosomal recessive centronuclear myopathy
BIN1	Orphanet:169189	Autosomal dominant centronuclear myopathy
SEMA3C	Orphanet:388	Hirschsprung disease
DST	Orphanet:314381	Hereditary sensory and autonomic neuropathy type 6
DST	Orphanet:412181	Epidermolysis bullosa simplex due to BP230 deficiency
SLC24A4	Orphanet:100032	Hypocalcified amelogenesis imperfecta
SLC24A4	Orphanet:100033	Hypomaturation amelogenesis imperfecta
SIK1	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
SIK1	Orphanet:697160	Infantile epileptic spasms syndrome
SORD	Orphanet:700508	Distal muscle weakness-foot deformity-elevated sorbitol level-hereditary motor neuropathy
SORL1	Orphanet:1020	Early-onset autosomal dominant Alzheimer disease
SPI1	Orphanet:33110	Autosomal non-syndromic agammaglobulinemia
SQSTM1	Orphanet:275864	Behavioral variant of frontotemporal dementia
SQSTM1	Orphanet:275872	Frontotemporal dementia with motor neuron disease
SQSTM1	Orphanet:603	Distal myopathy, Welander type
SQSTM1	Orphanet:803	Amyotrophic lateral sclerosis
STAG3	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
SYK	Orphanet:695807	Immunodeficiency-systemic inflammation-lymphoma predisposition syndrome
TCF7L2	Orphanet:528084	Non-specific syndromic intellectual disability
TNXB	Orphanet:230839	Classical-like Ehlers-Danlos syndrome type 1
TNXB	Orphanet:289365	Familial vesicoureteral reflux
TRH	Orphanet:238670	Isolated thyrotropin-releasing hormone deficiency
TRIP4	Orphanet:486811	Prenatal-onset spinal muscular atrophy with congenital bone fractures
TRIP4	Orphanet:486815	Congenital muscular dystrophy-respiratory failure-skin abnormalities-joint hyperlaxity syndrome
C1S	Orphanet:169147	Immunodeficiency due to a classical component pathway complement deficiency
C1S	Orphanet:75392	Periodontal Ehlers-Danlos syndrome
UBE2L3	Orphanet:536	Systemic lupus erythematosus
VCP	Orphanet:100070	Progressive non-fluent aphasia
VCP	Orphanet:275864	Behavioral variant of frontotemporal dementia
VCP	Orphanet:275872	Frontotemporal dementia with motor neuron disease
VCP	Orphanet:329475	Spastic paraplegia-Paget disease of bone syndrome

Cohort genes → proteins

74 cohort genes, 72 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	67
gwas_and_clinvar	5
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CLU	HGNC:2095	ENSG00000120885	P10909	Clusterin	gwas,clinvar
APOE	HGNC:613	ENSG00000130203	P02649	Apolipoprotein E	gwas,clinvar
APP	HGNC:620	ENSG00000142192	P05067	Amyloid-beta precursor protein	gwas,clinvar
MAPT	HGNC:6893	ENSG00000186868	P10636	Microtubule-associated protein tau	gwas,clinvar
PCDH11X	HGNC:8656	ENSG00000102290	Q9BZA7	Protocadherin-11 X-linked	gwas,clinvar
ECE2	HGNC:13275	ENSG00000145194	P0DPD6	Endothelin-converting enzyme 2	gencc
RORA	HGNC:10258	ENSG00000069667	P35398	Nuclear receptor ROR-alpha	gwas
BDH1	HGNC:1027	ENSG00000161267	Q02338	D-beta-hydroxybutyrate dehydrogenase, mitochondrial	gwas
RTN2	HGNC:10468	ENSG00000125744	O75298	Reticulon-2	gwas
BIN1	HGNC:1052	ENSG00000136717	O00499	Myc box-dependent-interacting protein 1	gwas
SDF2L1	HGNC:10676	ENSG00000128228	Q9HCN8	Stromal cell-derived factor 2-like protein 1	gwas
SEMA3C	HGNC:10725	ENSG00000075223	Q99985	Semaphorin-3C	gwas
SFSWAP	HGNC:10790	ENSG00000061936	Q12872	Splicing factor, suppressor of white-apricot homolog	gwas
ST6GAL1	HGNC:10860	ENSG00000073849	P15907	Beta-galactoside alpha-2,6-sialyltransferase 1	gwas
DST	HGNC:1090	ENSG00000151914	Q03001	Dystonin	gwas
SLC24A4	HGNC:10978	ENSG00000140090	Q8NFF2	Sodium/potassium/calcium exchanger 4	gwas
SLC28A1	HGNC:11001	ENSG00000156222	O00337	Sodium/nucleoside cotransporter 1	gwas
SLC4A8	HGNC:11034	ENSG00000050438	Q2Y0W8	Electroneutral sodium bicarbonate exchanger 1	gwas
SIK1	HGNC:11142	ENSG00000142178	P57059	Serine/threonine-protein kinase SIK1	gwas
SORD	HGNC:11184	ENSG00000140263	Q00796	Sorbitol dehydrogenase	gwas
SORL1	HGNC:11185	ENSG00000137642	Q92673	Sortilin-related receptor	gwas
SOX14	HGNC:11193	ENSG00000168875	O95416	Transcription factor SOX-14	gwas
SPI1	HGNC:11241	ENSG00000066336	P17947	Transcription factor PU.1	gwas
SPON1	HGNC:11252	ENSG00000262655	Q9HCB6	Spondin-1	gwas
SQSTM1	HGNC:11280	ENSG00000161011	Q13501	Sequestosome-1	gwas
STAG3	HGNC:11356	ENSG00000066923	Q9UJ98	Cohesin subunit SA-3	gwas
STK24	HGNC:11403	ENSG00000102572	Q9Y6E0	Serine/threonine-protein kinase 24	gwas
SYK	HGNC:11491	ENSG00000165025	P43405	Tyrosine-protein kinase SYK	gwas
TCF7L2	HGNC:11641	ENSG00000148737	Q9NQB0	Transcription factor 7-like 2	gwas
TIAM2	HGNC:11806	ENSG00000146426	Q8IVF5	Rho guanine nucleotide exchange factor TIAM2	gwas
CLEC3B	HGNC:11891	ENSG00000163815	P05452	Tetranectin	gwas
TNXB	HGNC:11976	ENSG00000168477	P22105	Tenascin-X	gwas
TOP1	HGNC:11986	ENSG00000198900	P11387	DNA topoisomerase 1	gwas
TRH	HGNC:12298	ENSG00000170893	P20396	Pro-thyrotropin-releasing hormone	gwas
ACP2	HGNC:123	ENSG00000134575	P11117	Lysosomal acid phosphatase	gwas
TRIP4	HGNC:12310	ENSG00000103671	Q15650	Activating signal cointegrator 1	gwas
UBA52P1	HGNC:12459			ubiquitin A-52 residue ribosomal protein fusion product 1 pseudogene 1	gwas
C1S	HGNC:1247	ENSG00000182326	P09871	Complement C1s subcomponent	gwas
UBE2L3	HGNC:12488	ENSG00000185651	P68036	Ubiquitin-conjugating enzyme E2 L3	gwas
VASP	HGNC:12652	ENSG00000125753	P50552	Vasodilator-stimulated phosphoprotein	gwas
VCP	HGNC:12666	ENSG00000165280	P55072	Transitional endoplasmic reticulum ATPase	clinvar
VLDLR	HGNC:12698	ENSG00000147852	P98155	Very low-density lipoprotein receptor	gwas
VSNL1	HGNC:12722	ENSG00000163032	P62760	Visinin-like protein 1	gwas
WNT3	HGNC:12782	ENSG00000108379	P56703	Proto-oncogene Wnt-3	gwas
LINC00158	HGNC:1283	ENSG00000185433	P58513	Putative uncharacterized protein encoded by LINC00158	gwas
ZNF12	HGNC:12902	ENSG00000164631	P17014	Zinc finger protein 12	gwas
ZNF224	HGNC:13017	ENSG00000267680	Q9NZL3	Zinc finger protein 224	gwas
ZNF273	HGNC:13067	ENSG00000198039	Q14593	Zinc finger protein 273	gwas
ZYX	HGNC:13200	ENSG00000159840	Q15942	Zyxin	gwas
ADAMTS9	HGNC:13202	ENSG00000163638	Q9P2N4	A disintegrin and metalloproteinase with thrombospondin motifs 9	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CLU	Clusterin	Functions as extracellular chaperone that prevents aggregation of non native proteins.
APOE	Apolipoprotein E	APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids.
APP	Amyloid-beta precursor protein	Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis.
MAPT	Microtubule-associated protein tau	Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity.
PCDH11X	Protocadherin-11 X-linked	Potential calcium-dependent cell-adhesion protein.
ECE2	Endothelin-converting enzyme 2	Converts big endothelin-1 to endothelin-1.
RORA	Nuclear receptor ROR-alpha	Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5’-AGGTCA-3’ preceded by a short A-T-rich sequence.
RTN2	Reticulon-2	Inhibits amyloid precursor protein processing, probably by blocking BACE1 activity.
BIN1	Myc box-dependent-interacting protein 1	Is a key player in the control of plasma membrane curvature, membrane shaping and membrane remodeling.
SEMA3C	Semaphorin-3C	Binds to plexin family members and plays an important role in the regulation of developmental processes.
SFSWAP	Splicing factor, suppressor of white-apricot homolog	Plays a role as an alternative splicing regulator.
ST6GAL1	Beta-galactoside alpha-2,6-sialyltransferase 1	Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates.
DST	Dystonin	Cytoskeletal linker protein.
SLC24A4	Sodium/potassium/calcium exchanger 4	Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) in exchange for 4 Na(+).
SLC28A1	Sodium/nucleoside cotransporter 1	Sodium and pyrimidine nucleoside symporter of the plasma membrane that imports uridine, thymidine and cytidine into cells by coupling their transport to the transmembrane sodium electrochemical gradient.
SLC4A8	Electroneutral sodium bicarbonate exchanger 1	Mediates electroneutral sodium- and carbonate-dependent chloride-HCO3(-) exchange with a Na(+):HCO3(-) stoichiometry of 2:1.
SIK1	Serine/threonine-protein kinase SIK1	Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, gluconeogenesis and lipogenesis regulation, muscle growth and differentiation and tumor suppression.
SORD	Sorbitol dehydrogenase	Polyol dehydrogenase that catalyzes the reversible NAD(+)-dependent oxidation of various sugar alcohols.
SORL1	Sortilin-related receptor	Sorting receptor that directs several proteins to their correct location within the cell.
SOX14	Transcription factor SOX-14	Acts as a negative regulator of transcription.
SPI1	Transcription factor PU.1	Pioneer transcription factor, which controls hematopoietic cell fate by decompacting stem cell heterochromatin and allowing other transcription factors to enter otherwise inaccessible genomic sites.
SPON1	Spondin-1	Cell adhesion protein that promotes the attachment of spinal cord and sensory neuron cells and the outgrowth of neurites in vitro.
SQSTM1	Sequestosome-1	Molecular adapter required for selective macroautophagy (aggrephagy) by acting as a bridge between polyubiquitinated proteins and autophagosomes.
STAG3	Cohesin subunit SA-3	Meiosis specific component of cohesin complex.
STK24	Serine/threonine-protein kinase 24	Serine/threonine-protein kinase that acts on both serine and threonine residues and promotes apoptosis in response to stress stimuli and caspase activation.
SYK	Tyrosine-protein kinase SYK	Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR).
TCF7L2	Transcription factor 7-like 2	Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner.
TIAM2	Rho guanine nucleotide exchange factor TIAM2	Modulates the activity of RHO-like proteins and connects extracellular signals to cytoskeletal activities.
CLEC3B	Tetranectin	Tetranectin binds to plasminogen and to isolated kringle 4.
TNXB	Tenascin-X	Appears to mediate interactions between cells and the extracellular matrix.
TOP1	DNA topoisomerase 1	Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex.
TRH	Pro-thyrotropin-releasing hormone	As a component of the hypothalamic-pituitary-thyroid axis, it controls the secretion of thyroid-stimulating hormone (TSH) and is involved in thyroid hormone synthesis regulation.
TRIP4	Activating signal cointegrator 1	Transcription coactivator which associates with nuclear receptors, transcriptional coactivators including EP300, CREBBP and NCOA1, and basal transcription factors like TBP and TFIIA to facilitate nuclear receptors-mediated transcription.
C1S	Complement C1s subcomponent	Component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the ad…
UBE2L3	Ubiquitin-conjugating enzyme E2 L3	Ubiquitin-conjugating enzyme E2 that specifically acts with HECT-type and RBR family E3 ubiquitin-protein ligases.
VASP	Vasodilator-stimulated phosphoprotein	Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance, lamellipodial and filopodial dynamics, platelet activation and cell migration.
VCP	Transitional endoplasmic reticulum ATPase	Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis.
VLDLR	Very low-density lipoprotein receptor	Multifunctional cell surface receptor that binds VLDL and transports it into cells by endocytosis and therefore plays an important role in energy metabolism.
VSNL1	Visinin-like protein 1	Regulates (in vitro) the inhibition of rhodopsin phosphorylation in a calcium-dependent manner.
WNT3	Proto-oncogene Wnt-3	Ligand for members of the frizzled family of seven transmembrane receptors.
ZNF12	Zinc finger protein 12	Transcriptional repressor which suppresses activation protein 1 (AP-1)- and serum response element (SRE)-mediated transcriptional activity.
ZNF224	Zinc finger protein 224	May be involved in transcriptional regulation as a transcriptional repressor.
ZNF273	Zinc finger protein 273	May be involved in transcriptional regulation.
ZYX	Zyxin	Adhesion plaque protein.
ADAMTS9	A disintegrin and metalloproteinase with thrombospondin motifs 9	Cleaves the large aggregating proteoglycans, aggrecan (at the ‘1838-Glu-|-Ala-1839’ site) and versican (at the ‘1428-Glu-|-Ala-1429’ site).
MS4A4A	Membrane-spanning 4-domains subfamily A member 4A	May be involved in signal transduction as a component of a multimeric receptor complex.
MS4A6A	Membrane-spanning 4-domains subfamily A member 6A	May be involved in signal transduction as a component of a multimeric receptor complex.
SLC2A9	Solute carrier family 2, facilitated glucose transporter member 9	High-capacity urate transporter, which may play a role in the urate reabsorption by proximal tubules.
ARFGAP2	ADP-ribosylation factor GTPase-activating protein 2	GTPase-activating protein (GAP) for ADP ribosylation factor 1 (ARF1).
MARK4	MAP/microtubule affinity-regulating kinase 4	Serine/threonine-protein kinase.

Protein-family classification

Druggable: 23 · Difficult: 13 · Unknown: 38 · Druggable fraction: 0.31

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	6	2.2×	0.658
Nuclear receptor	1	5.2×	0.832
Complement	1	3.6×	0.832
Scaffold/PPI	6	1.4×	0.832
Protease	3	1.5×	0.856
Ion channel	1	1.5×	0.882
Antibody/Immunoglobulin	3	1.2×	0.882
Phosphatase	1	1.1×	0.882
Transporter	1	1.1×	0.882
Other/Unknown	38	0.9×	0.882
Enzyme (other)	5	0.8×	0.882
Transcription factor	7	0.8×	0.882
GPCR	1	0.3×	0.958

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CLU	Other/Unknown	no		Clusterin-like, Clusterin_N, Clusterin_C
APOE	Other/Unknown	no		ApoA_E, Apolipoprotein_A1/A4/E
APP	Other/Unknown	no		Kunitz_BPTI, Amyloid_glyco_extra, Amyloid_glyco
MAPT	Other/Unknown	no		MAP_tubulin-bd_rpt, Tau, MAP2/MAP4/Tau
PCDH11X	Other/Unknown	no		Cadherin-like_dom, Cadherin_N, Protocadherin
ECE2	Protease	yes		Peptidase_M13, Peptidase_M13_N, Peptidase_M13_C
RORA	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
BDH1	Other/Unknown	no		SDR_fam, Sc_DH/Rdtase_CS, NAD(P)-bd_dom_sf
RTN2	Other/Unknown	no		Reticulon, RTN1-4
BIN1	Scaffold/PPI	no		SH3_domain, Amphiphysin, Amphiphysin_2
SDF2L1	Other/Unknown	no		MIR_motif, MIR_dom_sf
SEMA3C	Antibody/Immunoglobulin	yes		Semap_dom, Ig_sub, Ig-like_dom
SFSWAP	Other/Unknown	no		Surp, SWAP_N_domain, SWAP/Surp_sf
ST6GAL1	Enzyme (other)	yes	2.4.99.1	Glyco_trans_29, Sialyl_trans, GT29-like_sf
DST	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Actinin_actin-bd_CS
SLC24A4	Other/Unknown	no		K/Na/Ca-exchanger, NaCa_Exmemb, NCX_ion-bd_dom_sf
SLC28A1	Other/Unknown	no		CNT_N_dom, C_nuclsd_transpt, Gate_dom
SLC4A8	Other/Unknown	no		HCO3_transpt_euk, Na/HCO3_transpt, HCO3_transpt-like_TM_dom
SIK1	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
SORD	Enzyme (other)	yes	1.1.1.14	ADH_Zn_CS, GroES-like_sf, ADH-like_C
SORL1	Antibody/Immunoglobulin	yes		LDLR_classB_rpt, LDrepeatLR_classA_rpt, FN3_dom
SOX14	Transcription factor	no		HMG_box_dom, SOX_fam, HMG_box_dom_sf
SPI1	Other/Unknown	no		Ets_dom, WH-like_DNA-bd_sf, WH_DNA-bd_sf
SPON1	Other/Unknown	no		TSP1_rpt, Reeler_dom, Spondin_N
SQSTM1	Transcription factor	no		PB1_dom, Znf_ZZ, UBA-like_sf
STAG3	Other/Unknown	no		STAG, ARM-type_fold, SCD
STK24	Kinase	yes		Prot_kinase_dom, Kinase-like_dom_sf, Protein_kinase_ATP_BS
SYK	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
TCF7L2	Other/Unknown	no		HMG_box_dom, CTNNB1-bd_N, TCF/LEF
TIAM2	Scaffold/PPI	no		DH_dom, GDS_CDC24_CS, PDZ
CLEC3B	Other/Unknown	no		C-type_lectin-like, C-type_lectin-like/link_sf, CTDL_fold
TNXB	Antibody/Immunoglobulin	yes		EGF, Fibrinogen_a/b/g_C_dom, FN3_dom
TOP1	Enzyme (other)	yes	5.6.2.1	TopoI, TopoI_DNA-bd_euk, DNA_brk_join_enz
TRH	Other/Unknown	no		TRH
ACP2	Phosphatase	yes		His_Pase_clade-2, His_PPase_superfam, Acid_Pase_AS
TRIP4	Transcription factor	no		ASCH_domain, TRIP4/RQT4_C2HC5_Znf, PUA-like_sf
UBA52P1	Other/Unknown	no
C1S	Protease	yes	3.4.21.42	EGF-type_Asp/Asn_hydroxyl_site, Sushi_SCR_CCP_dom, CUB_dom
UBE2L3	Enzyme (other)	yes	2.3.2.23	UBC, UBQ-conjugating_enzyme/RWD, UBQ-conjugating_AS
VASP	Other/Unknown	no		WH1/EVH1_dom, PH-like_dom_sf, VASP_tetra
VCP	Enzyme (other)	yes	3.6.4.6	CDC4_N-term_subdom, AAA+_ATPase, ATPase_AAA_core
VLDLR	Other/Unknown	no		LDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, EGF
VSNL1	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS
WNT3	Other/Unknown	no		Wnt, Wnt3, Wnt_CS
LINC00158	Other/Unknown	no
ZNF12	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
ZNF224	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
ZNF273	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
ZYX	Transcription factor	no		Znf_LIM
ADAMTS9	Protease	yes		TSP1_rpt, Peptidase_M12B, Peptidase_M12B_N

Expression context

Cohort genes with no expression data: 1.

66 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	3
broad (>20)	70
unknown	1

Top tissues across cohort

Tissue	Cohort genes
monocyte	7
right lobe of liver	6
leukocyte	6
oocyte	6
calcaneal tendon	5
cortical plate	5
secondary oocyte	5
male germ line stem cell (sensu Vertebrata) in testis	4
right hemisphere of cerebellum	4
lateral nuclear group of thalamus	4
sural nerve	4
Brodmann (1909) area 23	4
apex of heart	4
right adrenal gland cortex	3
prefrontal cortex	3
superior frontal gyrus	3
liver	3
mucosa of transverse colon	3
gastrocnemius	3
hindlimb stylopod muscle	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CLU	294	ubiquitous	marker	lateral globus pallidus, calcaneal tendon, paraflocculus
APOE	267	ubiquitous	marker	left adrenal gland, left adrenal gland cortex, right adrenal gland cortex
APP	295	ubiquitous	marker	prefrontal cortex, renal medulla, Brodmann (1909) area 9
MAPT	141	broad	marker	cortical plate, superior frontal gyrus, prefrontal cortex
PCDH11X	74	broad	marker	cortical plate, male germ line stem cell (sensu Vertebrata) in testis, ganglionic eminence
ECE2	95	ubiquitous	marker	cerebellar hemisphere, right hemisphere of cerebellum, cerebellar cortex
RORA	284	ubiquitous	marker	upper leg skin, lateral nuclear group of thalamus, skin of hip
BDH1	134	ubiquitous	marker	right lobe of liver, liver, mucosa of transverse colon
RTN2	271	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, hindlimb stylopod muscle, gastrocnemius
BIN1	287	ubiquitous	marker	gastrocnemius, hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis
SDF2L1	199	ubiquitous	marker	mucosa of transverse colon, adenohypophysis, right lobe of liver
SEMA3C	289	ubiquitous	marker	mammary duct, synovial joint, calcaneal tendon
SFSWAP	291	ubiquitous	marker	sural nerve, tendon of biceps brachii, olfactory bulb
ST6GAL1	294	ubiquitous	marker	liver, right lobe of liver, renal medulla
DST	305	ubiquitous	marker	corpus callosum, calcaneal tendon, medial globus pallidus
SLC24A4	168	broad	marker	monocyte, leukocyte, primary visual cortex
SLC28A1	90	tissue_specific	marker	right lobe of liver, male germ line stem cell (sensu Vertebrata) in testis, liver
SLC4A8	219	ubiquitous	marker	pons, Brodmann (1909) area 23, superior vestibular nucleus
SIK1	138	not_expressed	marker	mucosa of stomach, skin of abdomen, zone of skin
SORD	199	ubiquitous	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
SORL1	293	ubiquitous	marker	frontal pole, paraflocculus, middle frontal gyrus
SOX14	15	tissue_specific	yes	placenta, hypothalamus, lower esophagus mucosa
SPI1	170	broad	marker	granulocyte, monocyte, leukocyte
SPON1	272	broad	marker	gall bladder, mucosa of sigmoid colon, pericardium
SQSTM1	241	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland
STAG3	185	broad	marker	oocyte, right testis, left testis
STK24	295	ubiquitous	marker	secondary oocyte, esophagus squamous epithelium, amniotic fluid
SYK	239	broad	marker	monocyte, mononuclear cell, leukocyte
TCF7L2	291	ubiquitous	marker	lateral nuclear group of thalamus, endothelial cell, pancreatic ductal cell
TIAM2	243	ubiquitous	yes	cortical plate, embryo, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 53.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
APP	11,686
VCP	10,015
MAPT	7,289
SQSTM1	7,269
APOE	6,793
SYK	5,172
TOP1	4,535
CLU	4,205
SORD	3,915
SPI1	3,823

Intra-cohort edges

A	B	Sources
ACP2	GAB2	intact
APOE	APP	intact, string_interaction
APOE	CLU	string_interaction
APOE	GAB2	string_interaction
APOE	MAPT	string_interaction
APOE	SORL1	string_interaction
APOE	SPON1	string_interaction
APOE	VLDLR	intact, string_interaction
APP	CLEC3B	biogrid_interaction
APP	CLU	intact, string_interaction
APP	ECE2	string_interaction
APP	MAPT	biogrid_interaction, intact, string_interaction
APP	MARK4	intact, string_interaction
APP	SORL1	biogrid_interaction, intact, string_interaction
APP	SPON1	intact, string_interaction
APP	ZNF224	intact
BCAS3	SLC2A9	string_interaction
BIN1	CLU	string_interaction
BIN1	MARK4	string_interaction
BIN1	MS4A4A	string_interaction
BIN1	MS4A4E	string_interaction
BIN1	MS4A6A	string_interaction
BIN1	MS4A6E	string_interaction
BIN1	SORL1	string_interaction
CD2AP	MS4A4A	string_interaction
CD2AP	MS4A4E	string_interaction
CD2AP	MS4A6A	string_interaction
CD2AP	MS4A6E	string_interaction
CD2AP	ZYX	biogrid_interaction
CLU	MS4A4A	string_interaction
CLU	MS4A4E	string_interaction
CLU	MS4A6A	string_interaction
CLU	MS4A6E	string_interaction
CLU	SORL1	string_interaction
CLU	VLDLR	string_interaction
GAB2	SORD	intact
GAB2	SYK	string_interaction
MAPT	MARK4	biogrid_interaction, string_interaction
MAPT	SIK1	biogrid_interaction
MRPL10	MRPL39	biogrid_interaction
MS4A4A	MS4A6E	string_interaction
MS4A4A	SORL1	string_interaction
MS4A4E	MS4A6A	string_interaction
MS4A4E	MS4A6E	string_interaction
MS4A4E	SORL1	string_interaction
MS4A6A	SLC24A4	string_interaction
MS4A6A	SORL1	string_interaction
MS4A6E	SORL1	string_interaction
SLC24A4	SPON1	biogrid_interaction
SORL1	SPON1	string_interaction

Structural data

PDB: 41 · AlphaFold-only: 31 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MAPT	P10636	293
APP	P05067	256
VCP	P55072	144
SYK	P43405	93
MRPL39	Q9NYK5	85
MRPL10	Q7Z7H8	84
STK24	Q9Y6E0	40
SPI1	P17947	35
APOE	P02649	29
VLDLR	P98155	27
SQSTM1	Q13501	26
UBE2L3	P68036	21
ZNF224	Q9NZL3	16
TOP1	P11387	15
C1S	P09871	14
CD2AP	Q9Y5K6	12
VASP	P50552	11
TRIP4	Q15650	10
GAB2	Q9UQC2	10
BIN1	O00499	7
SORL1	Q92673	7
SLC2A9	Q9NRM0	7
ST6GAL1	P15907	4
SPON1	Q9HCB6	4
CLEC3B	P05452	4
RORA	P35398	3
SORD	Q00796	3
TCF7L2	Q9NQB0	3
TNXB	P22105	3
CLU	P10909	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ACP2	P11117	92.09
SDF2L1	Q9HCN8	89.30
ECE2	P0DPD6	87.75
BDH1	Q02338	87.23
VSNL1	P62760	86.68
C1QTNF4	Q9BXJ3	86.63
STK32B	Q9NY57	86.38
SEMA3C	Q99985	85.69
FBXL7	Q9UJT9	82.67
SLC28A1	O00337	81.94
OR2B2	Q9GZK3	79.53
STAG3	Q9UJ98	78.46
MS4A6A	Q9H2W1	73.84
MS4A4A	Q96JQ5	73.38
SLC24A4	Q8NFF2	70.84
ZNF12	P17014	70.36
ZNF273	Q14593	70.23
ADAMTS9	Q9P2N4	69.47
SOX14	O95416	68.13
BCAS3	Q9H6U6	65.25
PCDH11X	Q9BZA7	64.22
MS4A6E	Q96DS6	63.77
ZYX	Q15942	63.57
NUAK1	O60285	62.48
MS4A4E	Q96PG1	61.59
SIK1	P57059	61.31
TRH	P20396	60.00
NPVF	Q9HCQ7	58.43
LINC00158	P58513	57.23
TIAM2	Q8IVF5	56.95

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 645. Enrichment computed across 250 evidence-associated genes (151 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 151 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective B3GALTL causes PpS	6	12.3×	0.003	SPON1, ADAMTS9, ADAMTS20, ADAMTS1, ADAMTS4, THSD7A
O-glycosylation of TSR domain-containing proteins	6	11.9×	0.003	SPON1, ADAMTS9, ADAMTS20, ADAMTS1, ADAMTS4, THSD7A
Cell-extracellular matrix interactions	4	17.8×	0.010	VASP, PARVB, FERMT2, LIMS2
Diseases associated with O-glycosylation of proteins	6	8.6×	0.010	SPON1, ADAMTS9, ADAMTS20, ADAMTS1, ADAMTS4, THSD7A
O-linked glycosylation	7	6.7×	0.010	ST6GAL1, SPON1, ADAMTS9, ADAMTS20, ADAMTS1, ADAMTS4, THSD7A
Diseases of glycosylation	6	5.2×	0.093	SPON1, ADAMTS9, ADAMTS20, ADAMTS1, ADAMTS4, THSD7A
Peptide ligand-binding receptors	8	3.9×	0.093	APP, TRH, ECE2, ACKR2, CCR2, CCR3, CCR5, CCRL2
Chemokine receptors bind chemokines	5	6.2×	0.100	ACKR2, CCR2, CCR3, CCR5, CCRL2
Diseases of metabolism	7	3.7×	0.198	SPON1, ADAMTS9, ADAMTS20, ADAMTS1, ADAMTS4, THSD7A, MMACHC
Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes	3	9.4×	0.210	RORA, SIK1, CRY2
Regulation of Complement cascade	4	6.2×	0.210	CLU, C1S, CR1, CR2
Amyloid fiber formation	6	4.1×	0.210	APOE, APP, SORL1, ADAM10, TSPAN14, APH1B
Class A/1 (Rhodopsin-like receptors)	7	3.4×	0.210	APP, ACKR2, CCR2, CCR3, CCR5, CCRL2, CHRM4
Signaling by GPCR	10	2.6×	0.210	APP, TIAM2, CAMK4, ACKR2, CCR2, CCR3, CCR5, CCRL2 (+2 more)
Disease	21	1.8×	0.230	APP, ST6GAL1, SLC24A4, SPON1, SQSTM1, SYK, TCF7L2, VCP (+13 more)
Incretin synthesis, secretion, and inactivation	2	13.8×	0.302	TCF7L2, SEC11C
NOTCH4 Activation and Transmission of Signal to the Nucleus	2	13.8×	0.302	ADAM10, APH1B
PINK1-PRKN Mediated Mitophagy	3	7.1×	0.302	SQSTM1, UBE2L3, TOMM40
Nuclear signaling by ERBB4	3	6.9×	0.302	APOE, YAP1, APH1B
GPCR ligand binding	7	3.0×	0.302	APP, ACKR2, CCR2, CCR3, CCR5, CCRL2, CHRM4
Metabolism of proteins	21	1.7×	0.304	APOE, APP, RORA, BDH1, ST6GAL1, SORL1, SPON1, SQSTM1 (+13 more)
Presynaptic nicotinic acetylcholine receptors	2	12.6×	0.308	CHRNA2, CHRNE
Defective SLC2A9 causes hypouricemia renal 2 (RHUC2)	1	75.6×	0.316	SLC2A9
Defective SLC24A4 causes hypomineralized amelogenesis imperfecta (AI)	1	75.6×	0.316	SLC24A4
Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters	2	11.6×	0.316	RORA, CRY2
RHO GTPase cycle	7	2.8×	0.316	TIAM2, VCP, ARFGAP2, CDC42EP3, RRAS2, SH3RF1, CDC42SE2
Signal Transduction	24	1.6×	0.316	APOE, APP, SQSTM1, SYK, TCF7L2, TIAM2, VCP, ARFGAP2 (+16 more)
Acetylcholine binding and downstream events	2	10.8×	0.317	CHRNA2, CHRNE
Postsynaptic nicotinic acetylcholine receptors	2	10.8×	0.317	CHRNA2, CHRNE
Signaling by NOTCH2	2	9.4×	0.361	ADAM10, APH1B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 224 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of amyloid-beta formation	6	23.8×	2e-04	CLU, APOE, RTN2, BIN1, SORL1, SPON1
positive regulation of amyloid fibril formation	3	45.1×	0.018	CLU, APOE, APP
immune complex clearance	2	75.2×	0.041	CLU, CR1
regulation of amyloid-beta clearance	2	75.2×	0.041	CLU, APOE
positive regulation of protein tyrosine kinase activity	3	28.2×	0.041	CASS4, LILRA5, CSF1R
microglial cell proliferation	3	25.1×	0.041	CLU, TREM2, CSF1R
regulation of mitochondrial transcription	3	25.1×	0.041	KAT8, MTRES1, KANSL1
positive regulation of non-canonical NF-kappaB signal transduction	6	6.8×	0.048	APP, VCP, C1QTNF4, TREM2, TRIM56, SASH1
negative regulation of activation of membrane attack complex	2	50.1×	0.068	CLU, CR1
collateral sprouting in absence of injury	2	50.1×	0.068	APP, COBL
ionotropic glutamate receptor signaling pathway	3	17.4×	0.068	APP, GRIN3A, GRIN3B
negative regulation of amyloid fibril formation	3	17.4×	0.068	CLU, APOE, TREM2
microglial cell activation	4	11.2×	0.068	CLU, APP, MAPT, TREM2
integrin-mediated signaling pathway	7	5.0×	0.068	DST, SYK, ZYX, FERMT2, LIMS2, ADAM10, ADAMTS1
positive regulation of tumor necrosis factor production	7	4.8×	0.070	CLU, APP, SYK, C1QTNF4, CCR2, LILRA5, ADAM10
axo-dendritic transport	2	37.6×	0.070	APP, KLC3
regulation of macrophage migration	2	37.6×	0.070	CCR2, CSF1R
adenosine to inosine editing	2	30.1×	0.070	ADAR, ADARB2
neuron recognition	2	30.1×	0.070	CNTNAP2, NTM
detection of lipopolysaccharide	2	30.1×	0.070	SCARB1, TREM2
very-low-density lipoprotein particle clearance	2	30.1×	0.070	APOE, VLDLR
positive regulation of melanocyte differentiation	2	30.1×	0.070	ADAMTS9, ADAMTS20
negative regulation of complement activation	2	30.1×	0.070	CLU, CR1
cellular response to lipoprotein particle stimulus	2	30.1×	0.070	APOE, TREM2
positive regulation of dendritic spine maintenance	2	30.1×	0.070	APOE, ZNF804A
regulation of amyloid precursor protein catabolic process	2	30.1×	0.070	APOE, PICALM
negative regulation of complement-dependent cytotoxicity	2	30.1×	0.070	CLU, CR1
prepulse inhibition	3	15.1×	0.070	CNTNAP2, GRIN3A, CTNNA2
interleukin-6-mediated signaling pathway	3	15.1×	0.070	SPI1, YAP1, ST18
astrocyte activation	3	13.3×	0.070	APP, MAPT, TREM2

Therapeutics

Drugs indicated for this disease

4 approved, 61 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Aducanumab	Approved (phase 4)
Donanemab	Approved (phase 4)
Lecanemab	Approved (phase 4)
Rivastigmine	Approved (phase 4)
Albumin Human	Phase 3 (in late-stage trials)
Aripiprazole	Phase 3 (in late-stage trials)
Atorvastatin	Phase 3 (in late-stage trials)
Azeliragon	Phase 3 (in late-stage trials)
Bapineuzumab	Phase 3 (in late-stage trials)
Bezisterim	Phase 3 (in late-stage trials)
Bifeprunox	Phase 3 (in late-stage trials)
Brexpiprazole	Phase 3 (in late-stage trials)
Caffeine	Phase 3 (in late-stage trials)
Celecoxib	Phase 3 (in late-stage trials)
Crenezumab	Phase 3 (in late-stage trials)
Cyanocobalamin	Phase 3 (in late-stage trials)
Doconexent	Phase 3 (in late-stage trials)
Donepezil	Phase 3 (in late-stage trials)
Elenbecestat	Phase 3 (in late-stage trials)
Encenicline	Phase 3 (in late-stage trials)
Ergocalciferol	Phase 3 (in late-stage trials)
Estrogen	Phase 3 (in late-stage trials)
Estrogens, Conjugated	Phase 3 (in late-stage trials)
Folic Acid	Phase 3 (in late-stage trials)
GV-971	Phase 3 (in late-stage trials)
Galantamine	Phase 3 (in late-stage trials)
Gantenerumab	Phase 3 (in late-stage trials)
Guanfacine	Phase 3 (in late-stage trials)
Haloperidol	Phase 3 (in late-stage trials)
Human Immunoglobulin G	Phase 3 (in late-stage trials)
Idalopirdine	Phase 3 (in late-stage trials)
Indomethacin	Phase 3 (in late-stage trials)
Intepirdine	Phase 3 (in late-stage trials)
Lanabecestat	Phase 3 (in late-stage trials)
Latrepirdine	Phase 3 (in late-stage trials)
Masitinib	Phase 3 (in late-stage trials)
Memantine	Phase 3 (in late-stage trials)
Methylphenidate	Phase 3 (in late-stage trials)
Modafinil	Phase 3 (in late-stage trials)
Neramexane	Phase 3 (in late-stage trials)
Nilotinib	Phase 3 (in late-stage trials)
Nilvadipine	Phase 3 (in late-stage trials)
OMEGA-3-ACID ETHYL ESTERS	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)
Progesterone	Phase 3 (in late-stage trials)
Pyridoxine	Phase 3 (in late-stage trials)
Remternetug	Phase 3 (in late-stage trials)
Rifampin	Phase 3 (in late-stage trials)
Risperidone	Phase 3 (in late-stage trials)
Rosiglitazone	Phase 3 (in late-stage trials)
Semagacestat	Phase 3 (in late-stage trials)
Semaglutide	Phase 3 (in late-stage trials)
Simufilam	Phase 3 (in late-stage trials)
Simvastatin	Phase 3 (in late-stage trials)
Solanezumab	Phase 3 (in late-stage trials)
Tarenflurbil	Phase 3 (in late-stage trials)
Tertomotide	Phase 3 (in late-stage trials)
Tramiprosate	Phase 3 (in late-stage trials)
Trazodone	Phase 3 (in late-stage trials)
Tricaprilin	Phase 3 (in late-stage trials)
Udenafil	Phase 3 (in late-stage trials)
Valiltramiprosate	Phase 3 (in late-stage trials)
Valproic Acid	Phase 3 (in late-stage trials)
Vitamin E	Phase 3 (in late-stage trials)
Xaliproden	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): 2-HYDROXYPROPYL-BETA-CYCLODEXTRIN, Acitretin, Aldesleukin, Arginine, Benfotiamine, Bexarotene, Brexanolone, Bumetanide, Buntanetap, Cannabidiol, Copper, Curcumin, Daratumumab, Epigalocatechin Gallate, Estradiol, Etanercept, Flutemetamol, Formoterol, Fosgonimeton, Ginkgo, INTERFERON BETA-1A, Iclepertin, Icosapent Ethyl, Inositol, Insulin Glulisine, Lecozotan, Lemborexant, Levetiracetam, Liraglutide, Lithium Carbonate, Lornoxicam, Masupirdine, Medroxyprogesterone Acetate, Mifepristone, Montelukast, Naproxen, Obicetrapib, Perindopril, Pioglitazone, Pramipexole, QS-21, Raloxifene, Rasagiline, Resveratrol, Rifaximin, Riluzole, Rofecoxib, Rotigotine, Sapropterin, Saracatinib, Sargramostim, Seltorexant, Serine, Sodium Chloride, Soybean Oil, Suvorexant, Tamibarotene, Telmisartan, Thalidomide, Thiethylperazine, Troriluzole, Varenicline, Verubecestat, Wax, Emulsifying, Zatolmilast.

Drug target analysis

Approved (phase 4): 14 · Phase ≥3: 16 · Phased (≥1): 16 · Undrugged: 58

Druggability breadth: 85 of 250 evidence-associated genes (34%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
APP	FLORBETAPIR F 18
MAPT	BEPRIDIL
RORA	TRETINOIN
SLC28A1	ADENOSINE
SIK1	FEDRATINIB
SORD	EPALRESTAT
STK24	NERATINIB
SYK	FEDRATINIB
TOP1	TOPOTECAN HYDROCHLORIDE
VCP	CLOTRIMAZOLE
MARK4	RIVASTIGMINE TARTRATE
CACNA1G	NIMODIPINE
STK32B	NERATINIB
NUAK1	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MAPT	449	4
SYK	54	4
APP	40	4
MARK4	22	4
NUAK1	22	4
SIK1	19	4
STK24	18	4
TOP1	12	4
CACNA1G	8	4
STK32B	5	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FLORBETAPIR F 18	4	APP
FLORBETAPIR	4	APP, MAPT
METHYLENE BLUE CATION	4	APP, MAPT
FLUTEMETAMOL F 18	4	APP
TRETINOIN	4	APP, MAPT, RORA
METHYLENE BLUE ANHYDROUS	4	APP, MAPT
CLIOQUINOL	4	APP, MAPT
DONEPEZIL	4	APP, MARK4
FLORBETABEN F18	4	APP
NIACIN	4	APP
FLUTEMETAMOL	4	APP
GENTIAN VIOLET	4	APP, MAPT
AMODIAQUINE	4	APP
CARVEDILOL	4	APP, MAPT
CHLOROQUINE	4	APP
TACRINE	4	APP, CACNA1G
RETINOL	4	APP, MAPT
BEPRIDIL	4	MAPT
PHENYLBUTAZONE	4	MAPT
CEFOTAXIME SODIUM	4	MAPT
DIENESTROL	4	MAPT
PROGESTERONE	4	MAPT
CLOTRIMAZOLE	4	MAPT, VCP
CHOLECALCIFEROL	4	MAPT
LATANOPROST	4	MAPT
CHLORTHALIDONE	4	MAPT
FLUORESCEIN	4	MAPT
OXCARBAZEPINE	4	MAPT
NABUMETONE	4	MAPT
GLIPIZIDE	4	MAPT

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
APP	1,744	Binding:1699, Functional:44, ADMET:1
TOP1	1,200	Binding:1161, Functional:38, ADMET:1
SYK	873	Binding:863, Functional:10
NUAK1	342	Binding:342
STK24	314	Binding:314
MARK4	246	Binding:245, Functional:1
SIK1	210	Binding:205, Toxicity:4, ADMET:1
MAPT	184	Binding:180, Functional:4
VCP	120	Binding:120
STK32B	118	Binding:118
RORA	115	Binding:111, Functional:3, Unclassified:1
CACNA1G	105	Binding:91, Functional:11, ADMET:2, Toxicity:1
C1S	30	Binding:28, Functional:2
ST6GAL1	27	Binding:27
TCF7L2	22	Binding:22
SQSTM1	20	Binding:20
SORD	17	Binding:16, Functional:1
SLC2A9	13	Binding:11, Functional:2
ECE2	9	Binding:9
SLC28A1	7	Binding:5, ADMET:2
WNT3	5	Functional:3, Binding:2
UBE2L3	2	Binding:2
VASP	2	Binding:2
ZYX	2	Binding:2
SLC24A4	1	Functional:1
CD2AP	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ST6GAL1	2.4.99.1	beta-galactoside alpha-(2,6)-sialyltransferase
SORD	1.1.1.14	L-iditol 2-dehydrogenase
SYK	2.7.10.2, 2.7.12.1	non-specific protein-tyrosine kinase, dual-specificity kinase
TOP1	5.6.2.1, 5.99.1.2	DNA topoisomerase, DNA topoisomerase
C1S	3.4.21.42	complement subcomponent C1s
UBE2L3	2.3.2.23, 2.3.2.24	E2 ubiquitin-conjugating enzyme, (E3-independent) E2 ubiquitin-conjugating enzyme
VCP	3.6.4.6	vesicle-fusing ATPase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
APP	1,744
MAPT	184
RORA	115
SIK1	210
STK24	314
SYK	873
TOP1	1,200
VCP	120
MARK4	246
CACNA1G	105
STK32B	118
NUAK1	342

Pharmacogenomics

Cohort genes with a PharmGKB record: 74; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

26 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
METHYLENE BLUE CATION	4	APP, MAPT
FLUTEMETAMOL F 18	4	APP
TRETINOIN	4	APP, MAPT, RORA
METHYLENE BLUE ANHYDROUS	4	APP, MAPT
CLIOQUINOL	4	APP, MAPT
FLORBETABEN F18	4	APP
NIACIN	4	APP
GENTIAN VIOLET	4	APP, MAPT
AMODIAQUINE	4	APP
CARVEDILOL	4	APP, MAPT
CHLOROQUINE	4	APP
TACRINE	4	APP, CACNA1G
RETINOL	4	APP, MAPT
BEPRIDIL	4	MAPT
PHENYLBUTAZONE	4	MAPT
CEFOTAXIME SODIUM	4	MAPT
DIENESTROL	4	MAPT
PROGESTERONE	4	MAPT
CLOTRIMAZOLE	4	MAPT, VCP
CHOLECALCIFEROL	4	MAPT
LATANOPROST	4	MAPT
CHLORTHALIDONE	4	MAPT
FLUORESCEIN	4	MAPT
OXCARBAZEPINE	4	MAPT
NABUMETONE	4	MAPT
GLIPIZIDE	4	MAPT

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	14	APP, MAPT, RORA, SLC28A1, SIK1, SORD, STK24, SYK, TOP1, VCP (+4 more)
B	Phased (≥1) drug, not yet approved	2	C1S, SLC2A9
C	Druggable family + PDB, no drug	5	ST6GAL1, SORL1, TNXB, UBE2L3, CSMD1
D	Druggable family + AlphaFold only, no drug	5	ECE2, SEMA3C, ACP2, ADAMTS9, OR2B2
E	Difficult family or no structure, no drug	48	CLU, APOE, PCDH11X, BDH1, RTN2, BIN1, SDF2L1, SFSWAP, DST, SLC24A4 (+38 more)

Undrugged target profiles

58 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
APOE	0	APP
SORL1	0	APP
SPON1	0	APP
CLU	0	—
PCDH11X	0	—
ECE2	9	—
BDH1	0	—
RTN2	0	—
BIN1	0	—
SDF2L1	0	—
SEMA3C	0	—
SFSWAP	0	—
ST6GAL1	27	—
DST	0	—
SLC24A4	1	—
SLC4A8	0	—
SOX14	0	—
SPI1	0	—
SQSTM1	20	—
STAG3	0	—
TCF7L2	22	—
TIAM2	0	—
CLEC3B	0	—
TNXB	0	—
TRH	0	—
ACP2	0	—
TRIP4	0	—
UBA52P1	0	—
UBE2L3	2	—
VASP	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3,050.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	482
PHASE3	244
PHASE1	126
PHASE4	116
PHASE1/PHASE2	78
PHASE2/PHASE3	49
EARLY_PHASE1	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00950430	PHASE4	ENROLLING_BY_INVITATION	Imaging of Brain Amyloid Plaques in the Aging Population
NCT03082755	PHASE4	RECRUITING	Nighttime Agitation and Restless Legs Syndrome in People With Alzheimer’s Disease
NCT03454646	PHASE4	NOT_YET_RECRUITING	Comparison of Therapeutic Strategies With Cholinesterase Inhibitors (SOS TRIAL)
NCT03821857	PHASE4	RECRUITING	Sex-Specific Effects of Endocrine Disruption on Aging and Alzheimer’s Disease
NCT05004987	PHASE4	RECRUITING	Aβ Dynamics in LLMD
NCT05058040	PHASE4	ACTIVE_NOT_RECRUITING	A Clinical Study to Evaluate the Long-Term Safety Sodium Oligomannate Capsules (GV-971)
NCT05181475	PHASE4	ACTIVE_NOT_RECRUITING	Long-term Efficacy and Safety Study of GV-971
NCT05908695	PHASE4	RECRUITING	An Efficacy and Safety Study of Sodium Oligomannate (GV-971) for the Treatment of Alzheimer’s Disease
NCT05924425	PHASE4	RECRUITING	Daridorexant to Treat Insomnia in Patients With Mild Cognitive Impairment and Mild to Moderate Alzheimer Disease
NCT06911944	PHASE4	NOT_YET_RECRUITING	Amyloid Lowering for Alzheimer’s in Down’s With Donanemab Investigation
NCT07034222	PHASE4	ACTIVE_NOT_RECRUITING	12-Month Real-World Safety & Efficacy of Lecanemab in Early Alzheimer’s Disease
NCT07579689	PHASE4	NOT_YET_RECRUITING	Effects of Ginkgo Biloba on Blood Biomarkers in Mild Cognitive Impairment
NCT07604896	PHASE4	RECRUITING	Evaluating the Efficacy and Safety of Lecanemab in Alzheimer’s Disease Through Multi-omics Approachs
NCT00009191	PHASE4	COMPLETED	The Depression in Alzheimer’s Disease Study (DIADS)
NCT00009217	PHASE4	COMPLETED	Treatment of Behavioral Symptoms in Alzheimer’s Disease
NCT00018278	PHASE4	COMPLETED	Electrophysiologic Measures of Treatment Response in Alzheimer Disease
NCT00035204	PHASE4	COMPLETED	A Study of the Effects on Sleep, Attention, and Gastrointestinal Tolerance of Galantamine and Donepezil in Patients With Alzheimer’s Disease
NCT00042172	PHASE4	COMPLETED	Treatment for Early Memory Loss
NCT00046358	PHASE4	COMPLETED	The Effect of Short-Term Statins and NSAIDs on Levels of Beta-Amyloid, a Protein Associated With Alzheimer’s Disease
NCT00104442	PHASE4	COMPLETED	Study of the Effects of Current Drug Treatments on Levels of Certain Brain Chemicals in Alzheimer’s Disease
NCT00120874	PHASE4	COMPLETED	Memantine and Comprehensive, Individualized Management of Alzheimer’s Disease and Caregiver Training
NCT00142324	PHASE4	UNKNOWN	CALM-AD
NCT00165724	PHASE4	COMPLETED	Alzheimer’s Disease Long-term Follow-up Study (ALF Study)
NCT00165750	PHASE4	TERMINATED	Correlation Between Regional Brain Volume and Response to Donepezil Treatment in AD Patients
NCT00202124	PHASE4	COMPLETED	Double Blind Study of Trp01 in Patients With Alzheimer’s Disease
NCT00208819	PHASE4	COMPLETED	A Comparison of Two Standard Therapies in the Management of Dementia With Agitation
NCT00216515	PHASE4	COMPLETED	The Efficacy of Galantamine on the Attention and the Frontal Function of the Patients With Dementia of Alzheimer Type
NCT00230568	PHASE4	COMPLETED	EARTH 413: A Study of Aricept in Hispanic Patients With Mild to Moderate Alzheimer’s Disease (AD)
NCT00234637	PHASE4	COMPLETED	Rivastigmine Monotherapy and Combination Therapy With Memantine in Patients With Moderately Severe Alzheimer’s Disease Who Failed to Benefit From Previous Cholinesterase Inhibitor Treatment
NCT00245206	PHASE4	COMPLETED	Side Effects of Newer Antipsychotics in Older Adults
NCT00254033	PHASE4	COMPLETED	Apathy Associated With Alzheimer’s Disease
NCT00260624	PHASE4	COMPLETED	Escitalopram Treatment of Patients With Agitated Dementia
NCT00303277	PHASE4	COMPLETED	Do HMG CoA Reductase Inhibitors Affect Abeta Levels?
NCT00305903	PHASE4	COMPLETED	Safety and Tolerability of Rivastigmine With Add-on Memantine in Patients With Probable Alzheimer’s Disease
NCT00306124	PHASE4	UNKNOWN	Dopaminergic Enhancement of Learning and Memory in Healthy Adults and Patients With Dementia/Mild Cognitive Impairment
NCT00334906	PHASE4	COMPLETED	Study of Memantine in Assessment of Selected Measures of Volumetric Magnetic Resonance Imaging (MRI) and Cognition in Moderate AD (Alzheimer’s Disease)
NCT00369603	PHASE4	TERMINATED	Functional Brain Imaging of Medication Treatment Response in Mild Alzheimer’s Disease Patients
NCT00375557	PHASE4	WITHDRAWN	Safety and Efficacy of Divalproex and Quetiapine in Elderly Alzheimer’s Dementia Patients
NCT00381381	PHASE4	COMPLETED	The Clinical Response of Choline Acetyltransferase and Apolipoprotein Epsilon Gene Polymorphisms to Donepezil in Alzheimer’s Disease
NCT00385684	PHASE4	COMPLETED	Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DONEPEZIL	4	87
RIVASTIGMINE	4	69
MEMANTINE	4	30
GALANTAMINE	4	27
FLORBETAPIR F 18	4	16
DONANEMAB	4	12
FLORTAUCIPIR F 18	4	10
LECANEMAB	4	8
ADUCANUMAB	4	6
CITALOPRAM	4	5
RISPERIDONE	4	5
BREXPIPRAZOLE	4	4
FLORBETABEN	4	4
GINKGO	4	4
ESTRADIOL	4	3
FLUTEMETAMOL	4	3
METHYLPHENIDATE	4	3
ROSIGLITAZONE MALEATE	4	3
SIMVASTATIN	4	3
VITAMIN E	4	3
ALBUMIN HUMAN	4	2
BUPROPION	4	2
DARIDOREXANT	4	2
DIVALPROEX SODIUM	4	2
DOXYCYCLINE	4	2
DOXYCYCLINE ANHYDROUS	4	2
DRONABINOL	4	2
ESCITALOPRAM	4	2
FLORBETAPIR	4	2
INSULIN DETEMIR	4	2