Although Alzheimer's is mostly considered a brain disorder, recent findings suggest the disease also affects other organs. Researchers at Baylor College of Medicine, the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital (Duncan NRI), and collaborating institutions have developed a new understanding of how Alzheimer's affects different tissues throughout the body using the fruit fly model. The findings, published in Neuron, provide new insights into brain-body communication in neurodegeneration and pave the way for the identification of new biomarkers and therapeutic targets for Alzheimer's disease.
“Alzheimer's disease is a neurodegenerative disorder characterized by the accumulation of amyloid plaques in the brain, containing the protein A?42, and tangles of thread-like structures of the tau protein. To better understand how the disease affects other organs in the body, we created an Alzheimer's fly cell atlas that profiles the genes expressed by individual cells from 219 cell types in the heads and bodies of Alzheimer's fruit flies,” said co-corresponding author Dr. Hongjie Li, assistant professor of molecular and human genetics and at Baylor University's Huffington Center on Aging. He is also a member of Baylor University's Dan L. Duncan Comprehensive Cancer Center.
The researchers generated Alzheimer's fruit flies by expressing A?42 or tau only in the neurons of adult flies. This approach avoids developmental effects and focuses on the characteristics of adult flies. They then examined changes in the brains and other organs of these modified flies.
“We found that the expression of A?42 or tau in neurons affected both neurons and other tissues in the fruit fly's body,” said co-first author Ye-Jin Park, a graduate student jointly mentored by Li and Dr. Hugo Bellen. “The expression of A?42 primarily affected the nervous system. Sensory neurons, which are involved in sight, hearing, and smell, were particularly vulnerable. A decline in the sense of smell can be an early symptom of Alzheimer's disease, and in this study, we identified specific olfactory neurons that were affected by A?42 in fruit flies.”
“On the other hand, tau expression in neurons led to significant changes, especially in peripheral tissues, such as altered fat metabolism and digestion, as well as reduced fertility. These changes resemble age-related changes and suggest that tau expression accelerates aging,” said co-first author Dr. Tzu-Chiao Lu , a postdoctoral fellow in the Li lab. “We found that neural connectivity and other factors that mediate brain-body communication were disrupted in tau flies.”
“These and other findings described in the Alzheimer’s Disease Fly Cell Atlas improve our understanding of the effects of the Alzheimer’s-associated proteins A?42 and tau on the entire organism,” said Bellen, a co-author of the work. Bellen is Distinguished Service Professor of Molecular and Human Genetics at Baylor University and the Horlock Professor of Neurogenetics at the Duncan NRI.
