Tau Protein Required for Development of Alzheimer’s Disease


May 15, 2002

Tau Protein Required for Development of Alzheimer’s Disease

CHICAGO— Researchers have argued for years over whether neurofibrillary tau tangles or beta-amyloid plaques are the primary cause of Alzheimer’s disease.

Autopsies show that these hallmarks of Alzheimer’s disease are often found in the same brain regions—preferentially in areas responsible for learning and memory—but investigators previously have been unable to identify a mechanism linking the two types of lesions.

Now, a group of Northwestern University neuroscientists have reported the first evidence showing that tau must be present to enable beta-amyloid to induce the degeneration of brain cells that occurs in Alzheimer’s disease.

Adriana Ferreira, MD, and co-researchers from The Feinberg School of Medicine and the Northwestern University Institute for Neuroscience recently published their findings, which support a key role for tau in the mechanisms leading to beta-amyloid–induced neurodegeneration, in an article in the April 30 issue of the Proceedings of the National Academy of Science.

Results of the group’s experiments showed that neurons with normal amounts of tau degenerated in the presence of beta-amyloid, while neurons specially treated to be devoid of tau did not degenerate.

“Our results underscore the importance of tau in the pathogenesis of this devastating disease and open a new chapter in deciphering the toxic pathways activated by beta-amyloid,” said Dr.Ferriera, assistant professor of cell and molecular biology and NUIN researcher.

When the researchers analyzed the composition of the cytoskeleton, or cellular scaffolding, of tau-depleted neurons, they found rapid turnover of microtubules, the structures within the cell that stabilize the cell’s shape and act as a sort of intracellular molecular transport system.

These results suggest that neurons that are able to maintain the composition of microtubules with rapid turnover as they age—that is, tau-depleted neurons—might be resistant to neurodegeneration, Dr. Ferreira said.

“These findings identify the dynamic behavior of the microtubules as a new target for therapeutic intervention. They also suggest that factors able to induce or restore a more plastic composition of the microtubules might prevent the neuronal degeneration associated with the formation of senile plaques in Alzheimer’s disease patients,” she said.

Currently, Dr. Ferreira and her laboratory group are testing a variety of such factors, including hormones and trophic factors.

Dr. Ferreira’s co-researchers on this study were Mark Rapoport, NUIN; Lester I. Binder, PhD, professor of cell and molecular biology and NUIN; as well as Hana N. Dawson, PhD, and Michael P. Vitek, PhD, Duke University, Durham, N.C., and Cognosci, Inc., Research Triangle Park, N.C.

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