Alzheimer's Disease: Genetics and Risk Factors - What You Need to Know

Alzheimer's disease (AD) is multifactorial. No single gene causes late-onset AD; it's polygenic + environmental.

Genetic Risk Factors

• APOE ε4: Strongest common risk allele. 1 copy → 2–3× risk; 2 copies → 8–12×. Not deterministic.
• Early-onset familial AD (<5%): Autosomal dominant mutations in APP, PSEN1, PSEN2 → near 100% penetrance, onset 30s–50s.
• Other loci: GWAS identified >40 risk loci (e.g., TREM2, CLU, BIN1) with small effects.

Non-Genetic Risk Factors

• Age (greatest), cardiovascular health, education/cognitive reserve, hearing loss, TBI, depression, social isolation, physical inactivity, diabetes, smoking, air pollution.

Protective Factors

• Mediterranean/MIND diet, exercise, cognitive engagement, social connection, sleep, vascular risk control.

Genetic Testing

• Not routine for late-onset (APOE ε4 not diagnostic).
• Considered for early-onset familial AD with genetic counseling.

Genetics loads the gun; lifestyle pulls the trigger. Healthy habits reduce risk even with genetic predisposition.