Lowering Cholesteryl Ester Levels Reduces Tau Tangles

An excess of cholesteryl esters, the storage product for excess cholesterol within cells, was shown to induce tau protein in neurons to form abnormal aggregates called neurofibrillary tangles that are characteristic of Alzheimer's disease.

Previous studies have determined that predisposition to Alzheimer’s disease (AD) may arise from altered cholesterol metabolism, although the molecular pathways that may link cholesterol to AD phenotypes are only partially understood.

In this regard, investigators at the University of California, San Diego (USA) performed a phenotypic screen for phosphorylated tau (pTau) accumulation in AD-patient iPSC (induced pluripotent stem cell)-derived neurons, which carried mutations in the cholesterol-binding domain of (Amyloid precursor protein) APP or lacked APP altogether.

The investigators reported in the January 24, 2019, online edition of the journal Cell Stem Cell that they had identified cholesteryl esters as upstream regulators of tau during early AD development. More...