Alzheimer’s discovery reveals dire effect of toxic tau protein on brain cells

by Active Bot
Alzheimer's art

In a revelatory breakthrough, scientists at the University of Virginia specializing in Alzheimer’s research have unveiled the intricate mechanism through which detrimental tau proteins inflict damage upon the fundamental operational directives of our brain cells.

This discovery not only sheds light on the enigma of tauopathies but also holds the potential for groundbreaking therapeutic approaches.

The malevolent protein, as discerned by the researchers, distorts the configuration of the nuclei within nerve cells, or neurons. This distortion, in turn, modifies the functionality of the genes encased within the nuclei, prompting a reprogramming of the cells to generate an excess of tau.

While the culpability of tau protein in Alzheimer’s and various neurodegenerative “tauopathies” has been long suspected, the recent research conducted by UVA’s Dr. George Bloom, Ph.D., along with his recently graduated protégé, Dr. Xuehan Sun, and their collaborators, marks one of the inaugural instances of pinpointing tangible physical detriments caused by tau to neurons.

This revelation not only tantalizes researchers with promising leads but also signifies a crucial step towards the development of novel treatments for Alzheimer’s disease and other currently untreatable tauopathies.

Dr. Bloom, from UVA’s Departments of Biology, Cell Biology, and Neuroscience, as well as the UVA Brain Institute, the Virginia Alzheimer’s Disease Center, and UVA’s Program in Fundamental Neuroscience, underscores the scarcity of knowledge regarding how toxic tau inflicts damage on neurons. He emphasizes that their research focuses on unraveling this critical aspect rather than delving into the well-explored territory of how toxic tau spreads between neurons in the brain.

Furthermore, Dr. Bloom suggests a potential avenue for intervention. The toxic tau is released from neurons, making interception plausible when it’s circulating in the brain outside of neurons. This interception could be achieved using antibodies or other pharmacological agents, offering a prospect to impede or halt the progression of Alzheimer’s disease and other tauopathies.

Tauopathies, characterized by the accumulation of tau in the brain, extend beyond Alzheimer’s disease to include conditions like frontotemporal lobar degeneration, progressive supranuclear palsy, and chronic traumatic encephalopathy. Presenting as dementia, personality shifts, and movement issues, non-Alzheimer’s tauopathies currently lack effective treatments. The UVA researchers, driven by a quest to comprehend the underlying dynamics, unveiled that tau “oligomers,” intricate assemblies of multiple tau proteins, exert profound effects on the usually smooth morphology of neuronal nuclei.

These oligomers induce a folding or “invagination” of the nuclei, disrupting the genetic material within. Given that the spatial arrangement of genes influences their function, this abnormal rearrangement can have severe consequences. The researchers observed changes in gene expression, notably a nearly threefold increase in the expression of the tau gene itself. This suggests a cascade effect where the presence of harmful tau prompts neurons to produce more of the same, akin to a snowball gathering momentum downhill.

Comparative analysis revealed that Alzheimer’s patients exhibited twice as many invaginated nuclei as those without the condition. Similar increases were observed in laboratory mice serving as models for Alzheimer’s and other tauopathies. The researchers contend that delving deeper into this process could pave the way for innovative strategies to prevent and treat Alzheimer’s and other tauopathies.

The comprehensive findings of this research have been published in the scientific journal Alzheimer’s & Dementia, ensuring open access for readers. The team, comprising researchers such as Xuehan Sun, Guillermo Eastman, Yu Shi, Subhi Saibaba, Ana K. Oliveira, John R. Lukens, Andrés Norambuena, Joseph A. Thompson, Michael D. Purdy, Kelly Dryden, Evelyn Pardo, James W. Mandell, and Dr. Bloom himself, maintains no financial interests in the work.

Support for this research was provided by the National Institutes of Health, grant RF1 AG051085; the Owens Family Foundation; the Cure Alzheimer’s Fund; Rick Sharp Alzheimer’s Foundation; Webb and Tate Wilson; and the NanoString nCounter Grant Program. Stay abreast of the latest medical research updates from UVA by subscribing to the Making of Medicine blog.

Source: University of Virginia Health System

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