Novel Treatment For Alzheimer’s Disease and Dementia

Pathological accumulation of phosphorylated Tau (pTau) and accumulation of amyloid-beta (Ab) fragments are the two major biochemical hallmarks of Alzheimer’s disease (AD). Effective strategies to remove Ab in AD-patient brains have been developed, but have not yet shown efficacy to slow cognitive decline in clinical trials. This finding has led to the idea that targeting Tau or combinatorial strategies that target both Tau and Ab are required to treat AD. Genetic, epidemiologic, and biochemical evidence suggests that predisposition to AD may arise from altered cholesterol metabolism, although the molecular pathways that may link cholesterol to AD phenotypes are only partially understood. Stimulation of a brain specific cytochrome that converts cholesterol to 24-hydroxycholesterol, which in turn reduces cholesteryl ester. Reduction of cholesteryl ester has been demonstrated to reduce pathological Tau phosphorylation in human neurons made from induced pluripotent stem cells. Also, low dose Efavirenz/Sustiva reduces neurofibrillary tangles in a mouse model. The pathway may run from cholesteryl ester to Tau via the proteasome. University of California, San Diego Office of Innovation and Commercialization licensing@ucsd.edu 858.534.5815