Scientists at Texas Children’s Duncan Neurological Research Institute (NRI) and Baylor College of Medicine have conducted a study that sheds new light on how certain genes associated with Alzheimer’s disease may impact the brain. The findings, published in the American Journal of Human Genetics, involved examining 100 fruit fly versions of human Alzheimer’s risk genes to better understand their role in brain structure, function, and stress resilience during aging.
Researchers used Drosophila melanogaster, commonly known as fruit flies, because these insects share many genetic similarities with humans and have short lifespans. By turning off specific genes in these flies, scientists observed how the loss affected brain health over time.
Dr. Joshua Shulman, co-director of the Duncan NRI at Texas Children’s and co-corresponding author of the study, stated: “We were very excited about the results. We found that most of the genes are expressed in the adult fly brain, including 24 specifically expressed in neurons and 13 in glia, another type of brain cell.”
The research identified 50 candidate Alzheimer’s risk genes that influence both brain structure and function in fruit flies. Of those, 18 caused signs of possible neurodegeneration when turned off. “One standout example was the gene Snx6, the fly version of human SNX32,” Shulman said. “When this gene was turned off, the flies developed holes in their brain tissue – a sign of neurodegeneration.”
Additionally, researchers found that 35 genes are necessary for proper electrical activity in neurons and eight for recovery from stress; disabling these led to symptoms like seizures or paralysis after exposure to heat or mechanical shock.
The team also investigated how these genes interact with amyloid-beta and tau proteins—both linked to Alzheimer’s damage in humans—and found that 28 altered how flies responded to these proteins.
Looking beyond individual genes, researchers grouped them by whether they caused structural damage, functional impairment or poor stress recovery. They compared these groups with patient data from people with Alzheimer’s disease. Shulman explained: “Different people seemed to carry risk genes from different groups. Some had genetic changes linked to brain structure problems, while others had genetic variations tied to stress resilience… This idea – called ‘causal heterogeneity’ – could help explain why Alzheimer’s looks different from person to person and why some treatments work for some people but not others.”
To support further research efforts on Alzheimer’s risk genes across species models like fruit flies and humans, the team has launched an online portal called ALICE (Alzheimer’s Locus Integrative Cross-species Explorer), available at https://alice.nrihub.org/.
This study involved multiple contributors affiliated with Texas Children’s Duncan NRI or Baylor College of Medicine. Funding was provided by several grants from the National Institutes of Health as well as other foundations such as Baylor Research Advocates for Student Scientists and BrightFocus Foundation.
Texas Children’s Hospital is a nonprofit healthcare organization focused on pediatric care, education and research throughout Texas and beyond. It includes specialized facilities like Texas Children’s Duncan NRI and works closely with Baylor College of Medicine.
