fbpx

Penn Medicine researchers discover a rare genetic form of dementia

A new, rare genetic form of dementia has been discovered by a team of Penn Medicine researchers. This discovery also sheds light on a new pathway that leads to protein build up in the brain — which causes this newly discovered disease, as well as related neurodegenerative diseases like Alzheimer’s Disease — that could be targeted for new therapies. The study was published today in Science.

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by a buildup of proteins, called tau proteins, in certain parts of the brain. Following an examination of human brain tissue samples from a deceased donor with an unknown neurodegenerative disease, researchers discovered a novel mutation in the Valosin-containing protein (VCP) gene in the brain, a buildup of tau proteins in areas that were degenerating, and neurons with empty holes in them, called vacuoles.

Abnormal neurofibrillary tangles (NFTs) — a buildup of tau protein in parts of the brain — helped Edward Lee, MD, PhD, an assistant professor of Pathology and Laboratory Medicine, and other Penn scientists uncover this new form of dementia.
Credit: Penn medicine

The team named the newly discovered disease Vacuolar Tauopathy (VT)–a neurodegenerative disease now characterized by the accumulation of neuronal vacuoles and tau protein aggregates.

“Within a cell, you have proteins coming together, and you need a process to also be able to pull them apart, because otherwise everything kind of gets gummed up and doesn’t work. VCP is often involved in those cases where it finds proteins in an aggregate and pulls them apart,” Edward Lee, MD, PhD, an assistant professor of Pathology and Laboratory Medicine in the Perelman School of Medicine at the University of Pennsylvania. “We think that the mutation impairs the proteins’ normal ability to break aggregates apart.”


Subscribe now to remove this ad, read unlimited articles, bookmark your favorite post and soo much more

The researchers noted that the tau protein they observed building up looked very similar to the tau protein aggregates seen in Alzheimer’s disease. With these similarities, they aimed to uncover how this VCP mutation is causing this new disease — to aid in finding treatments for this disease and others. Rare genetic causes of diseases can very often offer insight into more prevalent ones.


Sell and advertise your products and services for free on Ominy market. Click here to start selling now


READ MORE  Research: Music activates regions of the brain spared by Alzheimer's disease

The researchers first examined the proteins themselves, in addition to studying cells and an animal model, and found that the tau protein buildup is, in fact, due to the VCP mutation.

“What we found in this study is a pattern we’ve never seen before, together with a mutation that’s never been described before,” Lee said. “Given that this mutation inhibits VCP activity, that suggest the converse might be true — that if you’re able to boost VCP activity, that could help break up the protein aggregates. And if that’s true, we may be able to break up tau aggregates not only for this extremely rare disease, but for Alzheimer’s disease and other diseases associated with tau protein aggregation.”

Source:

University of Pennsylvania School of Medicine

Journal Reference:

Autosomal dominant VCP hypomorph mutation impairs disaggregation of PHF-tau

Abstract:
Neurodegeneration in Alzheimer’s disease (AD) is closely associated with accumulation of pathologic tau aggregates in the form of neurofibrillary tangles.

We found that a p.Asp395Gly mutation in VCP was associated with dementia characterized neuropathologically by neuronal vacuoles and neurofibrillary tangles. Moreover, VCP appeared to exhibit tau disaggregase activity in vitro which was impaired by the p.Asp395Gly mutation. Additionafsupplly, intracerebral microinjection of pathologic tau led to increased tau aggregates in p.Asp395Gly VCP knock-in mice compared to injected wild-type mice.


Subscribe now to remove this ad, read unlimited articles, bookmark your favorite post and soo much more

These findings suggest that p.Asp395Gly VCP is an autosomal dominant genetic mutation associated with neurofibrillary degeneration in part due to reduced tau disaggregation, raising the possibility that VCP may represent a therapeutic target for the treatment of AD.

Ominy science editory team

A team of dedicated users that search, fetch and publish research stories for Ominy science.

What do you think??

Enable notifications of new posts    OK No thanks