Genes Associated with Alzheimer's Disease
These genes affect Alzheimer's risk—but risk is not destiny. Environment and lifestyle powerfully modify genetic susceptibility.
Genetics explains ~60-80% of Alzheimer's risk variance—but that's not what you think it means.
High heritability doesn't mean genes are destiny. It means that among people with similar environments, genetic differences explain risk differences. Change the environment, and the risk equation changes. Lifestyle factors can override even APOE4 risk in many cases.
The genes.
Organized by biological function—what they actually do in the brain.
Lipid Transport & Clearance
The brain needs efficient lipid transport and debris clearance. These genes affect both.
The most significant genetic risk factor. APOE4 reduces amyloid clearance efficiency. But ~50% of E4/E4 carriers never develop Alzheimer's.
CLU (Clusterin)
Amyloid chaperoneHelps clear amyloid-beta from the brain. Variants affect clearance efficiency.
ABCA7
Lipid transportTransports lipids across cell membranes. Involved in amyloid processing and microglial function.
Immune & Microglial Function
The brain's immune cells (microglia) are critical for clearing debris. These genes affect their function.
TREM2
Microglial activationTriggers microglia to clear amyloid plaques. Rare variants significantly increase Alzheimer's risk.
CD33
Microglial inhibitionInhibits microglial phagocytosis. Some variants reduce CD33, which is protective.
MS4A cluster
Immune signalingFamily of genes involved in immune cell signaling. Multiple variants affect Alzheimer's risk.
Amyloid Processing
These genes directly affect how amyloid precursor protein is processed.
APP
Amyloid precursor proteinThe protein that gets cleaved into amyloid-beta. Rare mutations cause early-onset familial Alzheimer's.
PSEN1/PSEN2
Gamma-secretase componentsPart of the enzyme complex that cleaves APP. Mutations cause early-onset familial Alzheimer's.
Tau & Cytoskeleton
Tau tangles are the other hallmark of Alzheimer's. These genes affect tau and cellular structure.
MAPT
Tau proteinEncodes tau protein. While not a major Alzheimer's risk gene, tau pathology is central to the disease.
BIN1
Endocytosis & tau spreadingSecond strongest genetic risk factor after APOE. Affects how tau spreads between neurons.
Vascular & Metabolic
Brain health depends on blood flow and metabolism. These genes connect cardiovascular and brain health.
INPP5D
Immune signalingRegulates microglial function and inflammation. Connects immune and metabolic pathways.
SORL1
APP traffickingDirects APP away from amyloid-producing pathways. Low SORL1 increases amyloid production.
The APOE4 story.
APOE4 is the elephant in the room. Here's what the research actually shows.
The numbers in context
- • E4/E4 carriers: ~50% develop Alzheimer's by age 85. That means ~50% don't.
- • E3/E4 carriers: ~25-30% lifetime risk. Lower than you'd think.
- • Nigerian Yoruba with E4: Much lower Alzheimer's rates than American E4 carriers—same gene, different environment.
- • Exercise in E4 carriers: Can reduce risk to near-baseline levels in some studies.
Why APOE4 may have persisted
APOE4 was likely advantageous historically—better immune response to infections, improved fertility, and beneficial in high-pathogen environments. It's a mismatch with modern life (sedentary, high-sugar, sleep-deprived) that makes it problematic, not the gene itself.
What actually matters.
These factors can powerfully modify genetic risk—even for APOE4 carriers.
Sleep & Glymphatic Clearance
The brain clears amyloid during deep sleep. Poor sleep = poor clearance, regardless of genetics.
Metabolic Health
Type 2 diabetes doubles Alzheimer's risk. Insulin resistance impairs brain glucose use and increases inflammation.
Exercise & Blood Flow
Exercise increases BDNF, improves blood flow, and enhances clearance. One of the strongest protective factors.
Omega-3 & DHA
APOE4 carriers may need more DHA. The brain is 60% fat—it needs the right building blocks.
Inflammation
Chronic inflammation accelerates neurodegeneration. Anti-inflammatory lifestyle choices matter.
Cognitive Reserve
Education, social engagement, and mental stimulation build resilience against pathology.
"Alzheimer's genes don't cause Alzheimer's. They reveal a brain that needs different support to stay healthy."← Back to all genes