Protective Effects of Nicotinamide Adenine Dinucleotide and Related Precursors in Alzheimer’s Disease: A Systematic Review of Preclinical Studies

Data from preclinical studies propose nicotinamide adenine dinucleotide (NAD+) as a neuroprotective and bioenergetics stimulant agent to treat Alzheimer's disease (AD); however, there seems to be inconsistency between behavioral and molecular outcomes. We performed this systematic review to provide a better understanding of the effects of NAD+ in rodent AD models and to summarize the literature.Studies were identified by searching PubMed, EMBASE, Scopus, Google Scholar, and the reference lists of relevant review articles published through December 2020. The search strategy was restricted to articles about NAD+, its derivatives, and their association with cognitive function in AD rodent models. The initial search yielded 320 articles, of which 11 publications were included in our systematic review.Based on the primary outcomes, it was revealed that NAD+ improves learning and memory. The secondary endpoints also showed neuroprotective effects of NAD+ on different AD models. The proposed neuroprotective mechanisms included, but were not limited to, the attenuation of the oxidative stress, inflammation, and apoptosis, while enhancing the mitochondrial function.The current systematic review summarizes the preclinical studies on NAD+ precursors and provides evidence favoring the pro-cognitive effects of such components in rodent models of AD.