ApoE Mounts A Comeback In Alzheimer’s

After more than two decades of exploration, new research has identified apolipoprotein E (ApoE) as a potential direct regulator of transcription, suggesting a broad role for the molecule in the study of Alzheimer’s disease (AD) that could explain why the usual strategies of trying to break up accumulations of amyloid beta (Aβ) or regulate tau hyperphosphorylation have failed to adequately treat symptoms or cure the disease.

Using a combination of in vitro studies in neural cell lines, examination of skin cells from AD patients and analysis of mouse brain tissues into which human ApoE isoforms had been inserted, scientists from the Buck Institute for Research on Aging and the University of California, Los Angeles (UCLA) have shown that the ApoE4 isoform enters the cell nucleus and acts as a transcription factor for nearly 1,700 gene promoter regions, including dozens with known associations with AD