Alzheimer’s disease is a condition that causes dementia (memory loss), which starts very subtly and slowly becomes more severe. It can often impact an individual’s behavior, mood, cognition and, at times, can cause seizures and symptoms of Parkinson’s disease like tremors. There is no cure, but Alzheimer’s can be treated with medications and supportive care.
Who is at risk for Alzheimer’s Disease?
About 1% of people in their 60s may have a diagnosis of Alzheimer’s disease. For people in their mid-80s and beyond, the percentage rises sharply to 35-40%. A person at average risk has a 10-12% lifetime chance of developing Alzheimer’s. Factors that can increase risk include:
- Gender (women have a higher risk than men)
- Reduced physical and cognitive activity
- Vascular problems (high blood pressure, diabetes, high cholesterol, heart disease)
- Tobacco use
- Obesity
- Head trauma
The role of genes
One additional risk factor is a person’s genetic makeup. The vast majority (~75%) of those diagnosed with Alzheimer’s have no family history of the disease. Instead, their Alzheimer’s disease is likely to be related to one or more of the risk factors above. But if someone has a first degree relative (parent, child, sibling) with Alzheimer’s disease, it nearly doubles their chances of developing Alzheimer’s (20-25% lifetime risk vs. 10-12%).
Late vs. early onset
About 25% of people who develop Alzheimer’s have a family history of the disease. This form, called familial Alzheimer’s, is separated into two categories: late onset and early onset. A person is at risk for late onset familial Alzheimer’s if he or she has 1 or more family members diagnosed with Alzheimer’s after age 60 to 65. This form accounts for about 20% of cases. It is thought to be caused by multiple genetic factors plus environmental, diet, and lifestyle factors. Recent data suggests that more common variants identified in large genome-wide association studies may collectively contribute to late onset Alzheimer’s. Early onset Alzheimer’s accounts for about 5-10% of cases and often has a single gene cause.
Understanding the APOE gene
For the most part, there is no genetic testing that can be performed to make a formal diagnosis of late onset Alzheimer’s in an individual or family. However, there is one gene, called APOE, that has been linked to late onset familial disease. APOE is a gene that makes a protein called apolipoprotein E which is responsible for moving cholesterol and other fats in the blood. It is associated with high cholesterol and heart disease. Apolipoprotein E is also made in the brain and may be involved with the formation of amyloid plaques in the brain, one of the key drivers of AD. Individuals have two copies of the APOE gene (one from each parent) and the gene comes in three forms, called alleles: APOE ε2, APOE ε3 and APOE ε4. The APOE ε4 allele has been linked to the development of late onset familial Alzheimer’s.
It’s important to understand that risk numbers are just estimates — many people with one or two copies of the APOE ε4 allele never develop Alzheimer’s. This means that other factors in addition to the APOE ε4 contribute to late onset familial AD. Genetic testing for the APOE ε4 may be ordered to help confirm a diagnosis of Alzheimer’s disease, but it is typically not recommended to assess the risk of developing Alzheimer’s because of the unclear risks. However, some laboratories do include the APOE gene in their tests.
The genetics of early onset disease
Early onset familial Alzheimer’s is a relatively uncommon form of Alzheimer’s and accounts for 5-10% of all cases. This form is typically considered when two or more relatives have been diagnosed with Alzheimer’s before age 60. It is often caused by a single gene that is not working correctly (also known as a pathogenic variant).
At least three genes have been identified in early onset families: PSEN1, PSEN2, and APP. If an individual has a pathogenic variant in one of these three genes, there is a very high chance–but not 100%–that the individual will develop Alzheimer’s disease. That person’s children, siblings and parents all have a 50% chance of having the same mutated gene (this pattern is called autosomal dominant inheritance). Genetic testing can be done to help identify a risk factors for early onset familial Alzheimer’s. Although there is no cure, some people choose to undergo genetic testing for the early onset form to help with early diagnosis or interventions, participation in clinical trials, family planning, and/or financial/insurance planning.
The power of community support and advocacy
For individuals and families navigating Alzheimer’s disease, patient advocacy groups and online communities offer not only emotional support but also practical tools to better understand the condition, share experiences, and explore treatment options. Communities like PatientsLikeMe enable members to connect with others facing similar challenges — fostering a sense of empowerment and solidarity. Importantly, these groups can help amplify the voices of those affected by Alzheimer’s, driving awareness, promoting early detection, and accelerating research. Being part of a supportive community can make a profound difference for patients and families.
How Genome Medical can help
Genome Medical has genetic counselors with expertise in Alzheimer’s who can:
- talk to you about your risk
- help interpret previous genetic testing
- have a conversation about the risks and benefits of genetic testing for Alzheimer’s disease
If you’d like to schedule an appointment to speak to a genetic counselor, get started here.
- Genin E et al. APOE and Alzheimer disease: a major gene with semi-dominant inheritance. Molecular Psychiatry. 2011(16):903-907
- Qian J et al. APOE-related risk of mild cognitive impairment and dementia for prevention trials: An analysis of four cohorts. PLOS Medicine. 2017. DOI:10.1371/journal.pmed.1002254
- Andrews SJ, Renton AE, Fulton-Howard B, Podlesny-Drabiniok A, Marcora E, Goate AM. The complex genetic architecture of Alzheimer’s disease: novel insights and future directions. EBioMedicine. 2023 Apr;90:104511. doi: 10.1016/j.ebiom.2023.104511. Epub 2023 Mar 10. PMID: 36907103; PMCID: PMC10024184.
