Understanding the Genetics of Alzheimer’s Disease

What is Alzheimer’s Disease?

Alzheimer’s disease, the most common form of dementia, is a progressive condition that affects memory, cognition, and behavior. The condition develops as communication between brain cells breaks down due to the buildup of amyloid plaques (clumps of sticky protein fragments outside of cells) and neurofibrillary tangles (twisted strands of a protein called tau inside cells).

Most people associate Alzheimer’s with aging, and for good reason. Late-onset Alzheimer’s disease, which occurs after age 65, accounts for the vast majority of cases. However, early-onset Alzheimer’s disease, which occurs before age 65, accounts for about 10% of all Alzheimer’s cases. 

Is Alzheimer’s Disease Genetic?

Alzheimer’s disease risk can be influenced by things like age, lifestyle, medical history (like diabetes or heart disease), family history of Alzheimer’s, and yes…genetics. 

While late-onset Alzheimer’s disease tends to involve a mix of genetic and environmental factors, the early-onset form has a stronger genetic basis. This means that early-onset cases are more likely to be driven by high-impact inherited genetic changes.

Let’s break down the genetics for early-onset vs. late-onset Alzheimer’s disease.

Early-Onset Alzheimer’s Disease (EOAD)

About 5–10% of cases are caused by inherited genetic changes (also called mutations) in one of three key genes:

• APP
  

• PSEN1
  

• PSEN2 

Gene mutations in APP, PSEN1, and PSEN2 are inherited in an autosomal dominant manner, meaning that a person only needs one copy of the mutation to be at high risk. Carriers of these mutations often have a strong family history of Alzheimer’s and develop symptoms at a younger age, sometimes as early as their 30s or 40s.

It is important to note that these three genes do not explain many early-onset Alzheimer’s disease cases. That’s because we still have a lot to learn. Scientists estimate we only understand about one-third of all human genes, so the rest of the puzzle is still unfolding!

Late-Onset Alzheimer’s Disease (LOAD)

Late-onset Alzheimer’s disease, the more common form, is believed to result from a combination of factors like age, lifestyle, environment, and genetics. 

The best-known genetic contributor to late-onset Alzheimer’s disease is the APOE gene, which is involved in fat transport and metabolism.

There are three different versions of the APOE gene. These versions are named e2, e3, and e4. Since we inherit two copies of every gene, individuals can have any combination of these versions. For example, you could have inherited one e2 and one e4, while someone else has two e3s.

The impacts of each allele are summarized below:

The most important takeaway is this: APOE is a risk-modifier, not a diagnosis. Having the e4 allele does not mean you’ll definitely develop Alzheimer’s. Not having it doesn’t mean you’re “in the clear” either. It’s one piece of the puzzle, not the whole story.

So… Should I Get APOE Testing?

While APOE testing cannot answer, “Will I get Alzheimer’s or not?” or “What is the exact chance I get Alzheimer’s?”, APOE testing can help answer the question, “Does my APOE gene need some additional support?” 

For individuals with one or two e4 alleles, it can be important to prioritize:

• Supporting healthy cholesterol levels
  

• Reducing inflammation
  

• Promoting brain health through nutrition, exercise, and lifestyle

Knowing your APOE status can be helpful in the context of preventive and personalized care. At Golden Genetics, we use your genetics to create personalized protocols with actionable strategies for long-term brain health and wellness.

The genetics of Alzheimer’s disease is far from simple, but understanding your genetic makeup can empower you to take control of your health. Whether through rare, high-impact mutations or common risk alleles like APOE e4, genetic testing can help guide proactive lifestyle strategies and personalized care decisions.

References

Bennet, A. M., Di Angelantonio, E., Ye, Z., Wensley, F., Dahlin, A., Ahlbom, A., . . . de Faire, U. (2007). Association of apolipoprotein E genotypes with lipid levels and coronary risk. JAMA, 298(11), 1300-1311.

Cacace, R., Sleegers, K. and Van Broeckhoven, C. (2016), Molecular genetics of early-onset Alzheimer's disease revisited. Alzheimer's & Dementia, 12: 733-748.

Eichner, J. E., Dunn, S. T., Perveen, G., Thompson, D. M., Stewart, K. E., & Stroehla, B. C. (2002). Apolipoprotein E polymorphism and cardiovascular disease: a HuGE review. American Journal of Epidemiology, 155(6), 487-495.

Yassine, H. N., & Finch, C. E. (2020). APOE alleles and diet in brain aging and Alzheimer’s disease. Frontiers in Aging Neuroscience, 12, 150.