An international team of researchers led by Michael E. Belloy, PhD, an assistant professor of neurology and of psychiatry at WashU Medicine, identified key genetic targets for potential Alzheimer’s disease therapeutics development. Targeting specific genes in individuals would allow for more personalized approaches to Alzheimer’s disease prevention and treatment. Their findings were published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
APOE4, a variant of the apolipoprotein E (APOE) gene, accounts for roughly 50% of Alzheimer’s disease cases in older adults. Individuals with one or two copies of the APOE4 variant have anywhere from a 4-fold to 12-fold greater chance of developing Alzheimer’s compared to those without any copies of APOE4. But not everyone who is a carrier of the APOE4 gene develops the disease.
Belloy and colleagues, including first author Youjie Zeng, MD, PhD, a postdoctoral research associate in the Belloy lab, set out to understand what protects some APOE4 carriers from Alzheimer’s disease. To do this, they analyzed the genomes of nearly 450,000 individuals of European, African and Japanese ancestries, using pooled data from multiple genetic databases and public repositories. The authors identified 44 key genes that were associated with specific types of cells related to Alzheimer’s development, as well as specific drug candidates to target those genes. For instance, a large proportion of APOE4-associated genes were linked to a type of cell called oligodendrocytes, which are responsible for producing myelin (a protective layer around neurons) and enabling effective communication between neurons. This link suggests that treatments targeting genes related to oligodendrocytes in APOE4-positive individuals could help preserve myelination and protect against the effects of Alzheimer’s disease.
These and other recent findings by WashU Medicine researchers represent meaningful progress toward a treatment model where physicians identify the biological mechanisms driving Alzheimer’s in each individual and tailor prevention or treatment strategies accordingly.
Read more on the Department of Neurology website.
