Alzheimer’s disease is usually thought of as a brain disorder, but new research suggests its effects reach far beyond the brain. Scientists have discovered that this condition may also impact other organs throughout the body.

Using the laboratory fruit fly as a model, researchers from Baylor College of Medicine, the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, and partner institutions have uncovered how Alzheimer’s-related changes can spread across multiple tissues. Their findings, recently published in Neuron, could lead to the discovery of new diagnostic markers and more effective treatment strategies for Alzheimer’s disease.

“Alzheimer’s disease is a neurodegenerative disorder characterized by the accumulation in the brain of amyloid plaques containing the Aβ42 protein and tangles of thread-like structures of the Tau protein. To better understand how the disorder affects other organs in the body, we created an Alzheimer’s Disease Fly Cell Atlas, which profiles the genes expressed by single cells of 219 cell types in the heads and bodies of Alzheimer’s disease fruit flies,” said co-corresponding author Dr.  Hongjie Li, assistant professor of molecular and human genetics and the Huffington Center on Aging at Baylor. He also is a member of Baylor’s Dan L Duncan Comprehensive Cancer Center.

Modeling Alzheimer’s Disease in Flies

The researchers created Alzheimer’s disease fruit flies by expressing Aβ42 or Tau only in the neurons of adult flies. This approach avoids developmental effects and focuses on adult characteristics. Then, they assessed the presence of changes in the brains and other organs of these modified flies.

“We found that expressing Aβ42 or Tau in neurons affected both neurons and other tissues in the fruit fly body,” said co-first author Ye-Jin Park, a graduate student co-mentored by Li and Dr. Hugo Bellen. “Aβ42 expression primarily affected the nervous system. Sensory neurons involved in vision, audition, and olfaction 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 affected by Aβ42 in fruit flies.”

“On the other hand, Tau expression in neurons led to significant changes, mostly in peripheral tissues, for instance altered fat metabolism and digestion,n and reduced fecundity. These alterations mimic age-associated changes, suggesting that Tau expression accelerates aging,” said co-first author Dr. Tzu-Chiao Lu, a postdoctoral associate in the Li lab. “We found that neuronal connectivity and other factors that mediate brain-body communication were disrupted in Tau flies.”