A new study challenges the traditional view of Alzheimer's disease as solely a brain disorder. Researchers at Baylor College of Medicine and other institutions have discovered that Alzheimer's impacts the entire body. The study used fruit flies to examine the systemic consequences of Alzheimer's pathology.
The research focused on the toxic proteins Amyloid beta 42 (Aβ42) and Tau, which are hallmarks of Alzheimer's. Scientists engineered fruit flies to express human Aβ42 or Tau proteins in neuronal cells. This allowed them to study the effects of these proteins on different tissues.
The team created an Alzheimer's Disease Fly Cell Atlas using single-nucleus RNA sequencing (snRNA-seq). This atlas profiled the transcriptomes of 219 cell types in the flies' heads and bodies. The atlas revealed how Alzheimer's proteins disrupt cellular function beyond neurons.
Expression of Aβ42 mainly affected the nervous system. Sensory neurons for vision, hearing, and smell were particularly vulnerable. The loss of olfactory neurons aligns with the early symptom of reduced sense of smell in human Alzheimer's patients.
Tau protein expression caused changes in peripheral tissues, including fat metabolism and digestion. The study showed that Tau accelerated aging features, like impaired nutrient processing. Tau may also disrupt communication between the brain and distant tissues.
The Alzheimer's Disease Fly Cell Atlas is a valuable resource for neurodegeneration research. It allows researchers to explore the connection between brain pathology and other organ systems. This knowledge is crucial for developing new biomarkers and therapies that target the entire body.
The study highlights the power of using fruit flies as a model for complex human diseases. The research team included experts from Baylor College of Medicine, Texas Children's Hospital, and other universities. Their collaboration combined molecular genetics, neurobiology, and computational biology.
The findings suggest the development of systemic therapies for Alzheimer's. Targeting peripheral tissues or brain-body signaling could mitigate cognitive decline. Profiling vulnerable cell types may also lead to early diagnosis through biomarkers.
This research reshapes the understanding of Alzheimer's disease. By revealing the systemic impacts of Aβ42 and Tau proteins, the study paves the way for holistic approaches to diagnostics and therapeutics. The insights promise new strategies to address Alzheimer's as a multisystem disease.