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Office of Neuroscience Research > WUSTL Neuroscience News > Newly ID’d role of major Alzheimer’s gene suggests possible therapeutic target

Newly ID’d role of major Alzheimer’s gene suggests possible therapeutic target

Blocking ApoE4 in brain may prevent nerve cell death, inflammation

From the WashU Newsroom...

Nearly a quarter century ago, a genetic variant known as ApoE4 was identified as a major risk factor for Alzheimer’s disease — one that increases a person’s chances of developing the neurodegenerative disease by up to 12 times.

However, it was never clear why the ApoE4 variant was so hazardous. When the ApoE4 protein is present, clumps of the protein amyloid beta accumulate in the brain. But such clumps alone do not kill brain cells or lead to characteristic Alzheimer’s symptoms such as memory loss and confusion.

Now, a study led by researchers at Washington University School of Medicine in St. Louis shows that the presence of ApoE4 exacerbates the brain damage caused by toxic tangles of a different Alzheimer’s-associated protein: tau. In the absence of ApoE, tau tangles did very little harm to brain cells.

The findings suggest that targeting ApoE could help prevent or treat the brain damage present in Alzheimer’s disease, for which there are currently no effective therapies.

“Once tau accumulates, the brain degenerates,” said senior author David Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. “What we found was that when ApoE is there, it amplifies the toxic function of tau, which means that if we can reduce ApoE levels we may be able to stop the disease process.”

The study is published Sept. 20 in the journal Nature.

Alzheimer’s, which affects one in 10 people over age 65, is the most common example of a family of diseases called tauopathies. The group also includes chronic traumatic encephalopathy, which plagues professional boxers and football players, and several other neurodegenerative diseases.

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