Early-onset autosomal dominant Alzheimer disease: genes and variants
Explore variant evidence for Early-onset autosomal dominant Alzheimer disease across 3 analyzed proteins (PSEN1, PSEN2, APOE). Linked ClinVar records include 2 pathogenic or likely pathogenic variants, 0 variants of uncertain significance and 0 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Counts refer to the selected disease label.
Data updated 2026-10-10. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Early-onset autosomal dominant Alzheimer disease
PSEN1: Presenilin-1
Its catalytic activity within gamma-secretase cleaves APP and many other membrane proteins, including Notch receptors. Pathogenic variants alter amyloid-beta production and are the most common known cause of autosomal dominant early-onset Alzheimer disease.
2 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in PSEN1 have source records linked to Early-onset autosomal dominant Alzheimer disease. Association strength is not clinical gene validity.
PSEN2: Presenilin-2
Its gamma-secretase activity contributes to intramembrane cleavage of APP and other substrates in endolysosomal and cellular membranes. Pathogenic variants are a rare cause of autosomal dominant Alzheimer disease, generally with more variable penetrance and age of onset than PSEN1 variants.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in PSEN2 have source records linked to Early-onset autosomal dominant Alzheimer disease. Association strength is not clinical gene validity.
APOE: Apolipoprotein E
It redistributes cholesterol and other lipids between tissues by directing remnant lipoproteins to LDL-receptor-family members. The common epsilon4 isoform strongly increases late-onset Alzheimer disease risk and also influences plasma lipids and cardiovascular risk.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in APOE have source records linked to Early-onset autosomal dominant Alzheimer disease. Association strength is not clinical gene validity.
ClinVar pathogenic and likely pathogenic variants linked to Early-onset autosomal dominant Alzheimer disease
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| PSEN1 L282V | 282 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| PSEN1 L286V | 286 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
Same protein, different disease
- Alzheimer disease also has ClinVar records linked to PSEN1 variants; they fall mostly in different places as the Early-onset autosomal dominant Alzheimer disease variants (88 pathogenic / likely pathogenic).
- Frontotemporal dementia also has ClinVar records linked to PSEN1 variants; they fall mostly in different places as the Early-onset autosomal dominant Alzheimer disease variants (63 pathogenic / likely pathogenic).
- Acne inversa, familial, 3 also has ClinVar records linked to PSEN1 variants; they fall mostly in different places as the Early-onset autosomal dominant Alzheimer disease variants (57 pathogenic / likely pathogenic).
- Pick disease also has ClinVar records linked to PSEN1 variants; they fall mostly in different places as the Early-onset autosomal dominant Alzheimer disease variants (26 pathogenic / likely pathogenic).
Diseases related to Early-onset autosomal dominant Alzheimer disease
- Alzheimer disease, also linked to APOE, PSEN1 and PSEN2
- Dilated cardiomyopathy, also linked to PSEN1 and PSEN2
- Dementia, also linked to APOE and PSEN1
- Familial hypercholesterolemia, also linked to APOE
- Telangiectasia, hereditary hemorrhagic, type 2, also linked to PSEN1
- Frontotemporal dementia, also linked to PSEN1
- Acne inversa, familial, 3, also linked to PSEN1
- Type 2 diabetes mellitus, also linked to APOE
- Hyperlipoproteinemia, also linked to APOE
- Age related macular degeneration 9, also linked to APOE
- Diabetes, also linked to APOE
- Pick disease, also linked to PSEN1
Frequently asked questions
Which genes have records linked to Early-onset autosomal dominant Alzheimer disease?
This view contains 3 analyzed proteins: PSEN1, PSEN2, APOE. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 2 pathogenic or likely pathogenic variants, 0 variants of uncertain significance and 0 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 0 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 94 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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