Unfortunately, recent studies show that the effects of Alzheimer’s disease extend beyond the nervous system, affecting various organs and systems. This finding highlights the disease’s profound impact on biological aging, fat metabolism, and gut microbiome. In a new multidisciplinary study led by NYU researchers, the fruit-fly model was used to examine the disease’s peripheral effects. Their findings provide useful guidance for future research with other animals, including humans.
The research then looked in particular at how the Alzheimer’s-associated proteins, beta-42 and tau, impacted several bodily systems. Alzheimer’s has long been viewed as a solely brain-focused disease. According to this new study, it might induce a sort of accelerated aging phenotype across the rest of the body.
The authors of the new study noted, “For example, Alzheimer’s disease has been associated with disruptions in the gut microbiota, cardiovascular function, and hormone homeostasis.” This serves to further highlight the notion that Alzheimer’s disease does not only impact cognition, but it has a broader, systemic impact on physical health.
In describing this work, the crowning achievement is the creation of the Alzheimer’s Disease Fly Cell Atlas (AD-FCA). It’s based on a deep study of 219 cell types in flies that drive expression of proteins associated with Alzheimer’s. This novel expression system enables researchers to enhance or inhibit tau expression to study impacts on communication highways with peripheral doggy tissues.
These results showed that tau expression in fruit flies caused thousands of alterations in communication molecular roads. This result was especially surprising given the opposite results seen in amyloid and control flies. Such insights might eventually suggest new therapeutic strategies. Finally, they pledge to enhance our understanding of Alzheimer’s disease as a complicated systemic condition.
Gurneet Sawhney, MD, a chief neurosurgeon and founder at Neurolife Brain and Spine Clinic, commented on the broader implications of this research. He stated, “We often think of these proteins as brain-specific problems, but this work highlights how their impact may extend beyond the central nervous system. That’s an important shift in perspective for understanding the full systemic nature of dementia.”
Lactate dehydrogenase (LDH) is an important regulator of cellular energy metabolism. As such, it turned out to be a key part of the research. Dr. Sawhney explained that “its dysregulation can indicate tissue stress or damage. In the context of dementia, abnormal LDH activity might reflect broader metabolic dysfunction.”
This pioneering dementia research was made possible through the surprising value of fruit fly models in dementia research. As one researcher wrote recently, these models need not be so reductive. They do allow us to begin studying the impact of tau and amyloid at both genetic and cellular resolutions, providing quicker results with reduced complexity compared to mammalian models. This sparked further debate, but most importantly he stressed how these models have revealed important mechanisms of neurodegeneration. These discoveries usually carry over to mammalian systems down the road.
Alzheimer’s disease and its interactions with other body systems are increasingly becoming a research focus. Their goal is to create more targeted interventions that would help mitigate the wide-reaching impacts of this disease. This study demonstrates why it’s critical to understand the true cost and burden of Alzheimer’s disease in its entirety. It highlights the deep, urgent need to address its systemic nature.
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