NAD+ Reverses Alzheimer’s Deficits: Preclinical Findings

Synopsis

Alternative splicing defects are common features of aging and Alzheimer's disease (AD). This study identifies a previously unknown way that boosting NAD+ restores brain function: NAD+ helps correct widespread alternative splicing events (ASEs) by regulating EVA1C, a protein linked to neuronal development that is found in reduced levels in the AD hippocampus. Boosting NAD+ improved memory in AD mice with Tau buildup, but these benefits were lost when EVA1C was knocked down in the hippocampal CA1 region, showing that EVA1C is crucial for NAD+-mediated cognitive improvement. Our data suggest that the regulation of ASEs plays a major role in the therapeutic effects of NAD+ precursors like NR and NMN for treating AD. These findings highlight a NAD+–EVA1C splicing pathway that supports neuronal resilience and reduces AD pathology, suggesting that targeting RNA splicing could be a promising new treatment strategy for Alzheimer's and related diseases.

Journal

Science Advances