Fruit Flies Offer New Insights into Alzheimer's Disease Risk Genes

Scientists at Baylor College of Medicine have made significant progress in understanding how human Alzheimer's disease risk genes affect the brain. By studying fruit fly versions of 100 human Alzheimer's disease risk genes, researchers were able to determine the effects of these genes on the fly's brain structure, function, and stress resilience as the flies aged. The findings provide new insights into the complex mechanisms underlying Alzheimer's disease and could accelerate the study of the disease.

Key Takeaways:

• Researchers identified hundreds of genes that may increase the risk of developing Alzheimer's disease, but the roles these genes play in the brain were poorly understood.
• Scientists studied fruit fly versions of 100 human Alzheimer's disease risk genes and found that most of the genes were expressed in the adult fly brain, including 24 specifically expressed in neurons and 13 in glia.
• The team identified 50 candidate Alzheimer's disease risk genes in flies that were involved in both brain structure and function, including 18 that caused possible neurodegeneration when turned off.
• The researchers also found that 35 genes were required for proper electrical activity of neurons and eight for the ability of the flies to recover from stress.
• The study suggests that different individuals may develop Alzheimer's disease through distinct biological pathways, which could help explain why the disease looks different from person to person and why some treatments work for some people but not others.
• The team created a portal called ALICE (Alzheimer's Locus Integrative Cross-species Explorer) to provide access to the functional data generated in this study for other researchers to explore.

Statistics:

• 100 human Alzheimer's disease risk genes were studied in fruit flies.
• 50 candidate Alzheimer's disease risk genes were identified in flies that were involved in both brain structure and function.
• 18 genes caused possible neurodegeneration when turned off in flies.
• 35 genes were required for proper electrical activity of neurons in flies.
• 8 genes were required for the ability of flies to recover from stress.
• 28 genes changed how flies responded to amyloid-beta or tau.

Sources:

• Baylor College of Medicine
• Jan and Dan Duncan Neurological Research Institute (Duncan NRI) at Texas Children's Hospital
• American Journal of Human Genetics (https://www.cell.com/ajhg/fulltext/S0002-9297(25)00394-5)