Researchers closer to understanding how Alzheimer’s gene works

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The allele apolipoprotein E ε4 (APOE ε4) is the greatest genetic risk factor for Alzheimer’s disease (AD), but the role of the ApoE4 protein in AD has long been elusive. Turns out, ApoE4 may function as a transcription factor, according to a study published January 20 in the The Journal of Neuroscience, led by investigators at the Buck Institute for Aging Research and the University of California, Los Angeles (UCLA).

Study coauthors Rammohan Rao of the Buck Institute for Research on Aging and Dale Bredesen of the Buck Institute and UCLA “have provided evidence for a novel—in fact, radical—idea: that ApoE somehow gains access to the nucleosol and acts as a conventional transcription factor, influencing the expression of a large number of genes,” Steven Barger, who studies neurodegenerative disease at the University of Arkansas for Medical Sciences and was not involved in the study, wrote in an email to The Scientist.

Robert Mahley, a pioneer of ApoE research who also was not involved in the work, called the paper’s conclusions “very, very exciting.”

ApoE, a protein that is secreted from cells via vesicles, is known not only for its roles in neurodegenerative diseases but also for its functions in lipid metabolism and transport. Previously, other researchers reported that ApoE4 seemed to reduce the clearance of amyloid-β, the protein that clumps together to form the hallmark plaques of AD, from the brain in a mouse model.

Read full, original post: Another Role for ApoE?

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