ABOUT ALZHEIMER'S & DEMENTIA RISK

You've watched this disease in your family. Now you're asking whether it's in your future — and that question deserves more than uncertainty.

Whole genome sequencing reveals your APOE status, screens for early-onset familial variants, and contextualizes your dementia risk within a complete genetic picture.

APOE
PSEN1
PSEN2

About this condition

Alzheimer's & Dementia Risk

Alzheimer's disease is the most common cause of dementia, accounting for 50–60% of all dementia cases and affecting over 50 million people worldwide. Two distinct genetic forms exist: early-onset familial AD (less than 65 years, ~5–10% of all cases) caused by highly penetrant autosomal dominant variants in PSEN1, PSEN2, or APP, with onset sometimes as early as the 30s; and late-onset AD (over 65 years, ~90% of cases), which has a complex genetic architecture. APOE ε4 is the most significant known genetic risk factor for late-onset disease, but the presence of APOE ε4 influences risk — it does not predict or cause Alzheimer's.

APOE ε4 status modulates lifetime dementia risk significantly: carrying one copy of APOE ε4 doubles to triples risk compared to ε3/ε3 genotype; carrying two copies increases risk 8–12-fold. First-degree relatives of people with Alzheimer's disease have a cumulative lifetime dementia risk of 20–25% compared to approximately 10% in the general population. However, many ε4 carriers never develop dementia, and many people without ε4 do develop Alzheimer's disease — genetics influences but does not determine outcome.

Early-onset familial disease caused by PSEN1 or PSEN2 pathogenic variants follows autosomal dominant inheritance with ~100% penetrance — a diagnosis is definitive. For late-onset disease, APOE status alone provides incomplete information. APOE ε4 results require careful genetic counseling context because the risk is probabilistic, not deterministic. A genetic diagnosis enables enrollment in prevention trials, informed decision-making about lifestyle modifications, and reproductive counseling. Understanding your genetic status enables personalized prevention strategies before symptoms appear.

Gene locus: APOE (19q13.32) — ε4 allele; PSEN1 (14q24.2); PSEN2 (1q42.13)

APOE testing alone misses early-onset variants and hundreds of risk loci. WGS captures the full genetic picture of dementia risk.

APOE testing alone leaves you with an incomplete picture

Direct-to-consumer APOE genotyping provides a single data point without clinical context. APOE ε4 testing does not detect the dozens of additional genetic loci identified by GWAS studies that collectively contribute to dementia risk, nor does it capture protective variants in APOE itself (e.g., the Christchurch variant, APOE ε3-R136S, which appears protective). For families with early-onset Alzheimer's, APOE testing entirely misses pathogenic variants in PSEN1, PSEN2, or APP that cause highly penetrant familial disease. Whole genome sequencing captures APOE genotype, complete PSEN1/PSEN2 sequencing, and all GWAS loci — enabling polygenic risk scoring far more predictive than APOE alone.

A genetic finding enables prevention and eligibility for emerging therapies

A pathogenic PSEN1 or PSEN2 variant confirms early-onset familial Alzheimer's and enables presymptomatic testing of at-risk relatives, enrollment in prevention trials like DIAN-TU, and reproductive counseling. APOE ε4 status informs prevention-oriented decisions: cardiovascular health optimization, cognitive engagement, exercise, and medication choices. For example, APOE ε4 homozygotes have higher risk of amyloid-related imaging abnormalities (ARIA) with anti-amyloid therapies like lecanemab, which guides dosing and monitoring decisions. Genetic status transforms dementia from an uncontrollable inheritance into a modifiable risk.

One test. A lifetime of answers.

One kit, sent to your home. Your entire genome sequenced at the clinical standard used for diagnostic decisions. 200+ physician-ready reports delivered to your Genome Manager in 6–8 weeks — permanent and updated as science advances.

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