2024 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)

Therapeutic potential of nicotinic acid in PS19 tauopathy mice

Could a specific nutrient reduce the hallmark brain changes associated with Alzheimer’s?

Israel Coronel-Morales, Ph.D.
Indiana University
Indianapolis, IN - United States

Background

Recent studies have shown that a dietary intake of nicotinic acid (also called niacin), a component of vitamin B3, may be associated with a lower risk of cognitive decline and also Alzheimer’s. In brain cells, nicotinic acid activates a specific protein called HCAR2, which can be found in high levels in the brains of people with Alzheimer’s. However, the mechanisms linking nicotinic acid and reduced Alzheimer’s risk are unknown. 

Two of the hallmark brain changes that occur in Alzheimer’s are the accumulation of amyloid beta and tau protein to form amyloid plaques and tau tangles, respectively. In preliminary studies, Dr. Israel Coronel Morales and colleagues found that administering niacin, and thereby activating HCAR2, to genetically engineered Alzheimer’s-like mice that accumulate amyloid plaques slowed the progression of the disease compared to mice that did not receive the niacin.

Research Plan

Building on their initial studies, Dr. Morales and the team will expand on these findings and examine the impact of HCAR2 activation on Alzheimer’s progression in genetically engineered Alzheimer’s-like mice that develop tau tangles. The researchers will do this by first changing the levels of HCAR2 in the microglia, the brain’s primary immune cells, of these mice and measuring the impact on tau tangle accumulation. Next, they will treat the same mice with niacin and perform cognitive assessments to examine the impact of HCAR2 activation on Alzheimer’s progression.

Impact

Results of this study may shed new light on the role of HCAR2 in Alzheimer’s, and its therapeutic potential. If successful, the findings could serve as a foundation for clinical trials to evaluate niacin as a novel therapy to slow the progression of Alzheimer’s.