APOE Gene Variant Increases Alzheimer's Risk, But Many Without It Still Show Signs of the Disease
A recent study presented at the National Society of Genetic Counselors (NSGC) conference in 2025 has shed light on the intricate nature of Alzheimer's disease (AD) risk assessment and the crucial role of genetic counselors in deciphering biomarker test results.
The study revealed that individuals carrying the APOE ϵ4/ϵ4 gene variant had a significantly higher likelihood of exhibiting biomarkers indicating mild cognitive impairment or AD-associated dementia. This finding reinforces the established link between APOE ϵ4 and increased Alzheimer's risk. But here's where it gets intriguing: a considerable number of individuals lacking the APOE ϵ4 allele also displayed biomarker evidence of Alzheimer's pathology, emphasizing the complexity of interpreting these tests.
The research, led by Matt Tschirgi, MS, CGC, involved analyzing data from 21,267 individuals who underwent beta-amyloid testing. Approximately 27.1% of them were classified as higher risk, aligning with previous studies. Interestingly, no significant differences were found between individuals homozygous for APOE ε3 and APOE ε4.
In this study, researchers examined the results of APOE allele testing and biomarker levels in adults across the United States and its territories. They employed a specific method for APOE genotyping and reported biomarker levels as previously established.
Among 7313 individuals tested for p-tau 181, nearly 50% showed results consistent with mild cognitive impairment or AD-related dementia. Notably, participants homozygous for APOE ε4 had significantly higher biomarker results indicating MCI or dementia compared to those without the ε4 allele.
When examining p-tau 217 results in 743 individuals, over half exhibited signs of MCI or dementia due to AD. Interestingly, this proportion was similar between participants homozygous for APOE ε3 and APOE ε4. The authors suggest that genetic counselors can play a vital role in interpreting conflicting or ambiguous results, enabling informed decision-making, especially as new AD therapies emerge.
The increasing focus on Alzheimer's disease, driven by novel therapies, biomarker testing, and recent publications, has sparked discussions about the role of genetic counselors in testing. While APOE allele status is a well-known genetic risk factor for late-onset AD, the study authors highlight the complexity of counseling discussions due to the availability of newer blood biomarker assays.
This study underscores the importance of genetic counseling in navigating the complexities of Alzheimer's disease risk assessment, especially with the evolving landscape of biomarker testing and emerging therapies.
What are your thoughts on the role of genetic counselors in interpreting biomarker test results for Alzheimer's disease? Do you think their involvement is crucial for informed decision-making, or should the interpretation be left solely to medical professionals?
