Alternate view for pathology of AD

A new paper from researchers at the Case Western Reserve University School of Medicine challenges the classic theory that the nerve tangles seen in the brains of Alzheimer's disease (AD) victims are the cause of the disease, but rather proposes that they are a protective response to the disease. Their paper appears in the April issue of the journal Trends in Molecular Medicine.

The tangles, called neurofibrillary tangles (NFTs) by scientists, are one of the major features seen in brains of people with AD. The major component of NFTs is a protein called tau which has undergone a biochemical reaction called phosphorylation, and it is widely assumed that NFTs are central to the progression of AD and nerve cell death. Yet these tangles also occur to some extent in all brains with age although typically there are a lot more in the brains of people with AD.

"However, the correlation between the presence of NFTs and incidence of disease does not necessarily dictate a causal relationship" said lead author, Hyoung-gon Lee, Ph.D., a research associate in the Department of Pathology at Case. "In fact, since NFTs are produced in response to a variety of disease conditions, there is the distinct possibility that tau phosphorylation has an alternate role in disease - one that proceeds rather than precedes it."

So, what evidence is there to support a non-pathogenic role for NFTs in AD?

First of all, according to the researchers, tau phosphorylation or fibril formation itself is unlikely to be the harbinger of neuronal death since NFT-bearing neurons appear to survive for decades. In fact, one study found that neurons containing NFTs can survive for as long as 20 years.

Senior author, Mark A. Smith, Ph.D., professor of pathology at Case, noted, "These findings are in accord with our own published findings showing that NFTs are not only a relatively late event in the chronology of the disease, occurring decades after oxidat

Contact: George Stamatis
Case Western Reserve University

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