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.

来自临床前研究的数据表明，烟酰胺腺嘌呤二核苷酸 (NAD ⁺ ) 作为一种神经保护和生物能量刺激剂来治疗阿尔茨海默病 (AD)；然而，行为和分子结果之间似乎不一致。我们进行了这项系统审查，以更好地了解 NAD ⁺在啮齿动物 AD 模型中的影响并总结文献。

通过搜索 PubMed、EMBASE、Scopus、Google Scholar 以及截至 2020 年 12 月发表的相关评论文章的参考列表来确定研究。搜索策略仅限于关于 NAD ⁺及其衍生物及其与 AD 啮齿动物认知功能关联的文章楷模。最初的搜索产生了 320 篇文章，其中 11 篇出版物被纳入我们的系统评价。

根据主要结果，发现 NAD ⁺可改善学习和记忆。次要终点还显示 NAD ⁺对不同 AD 模型的神经保护作用。提出的神经保护机制包括但不限于氧化应激、炎症和细胞凋亡的减弱，同时增强线粒体功能。

当前的系统评价总结了 NAD ⁺前体的临床前研究，并提供了支持这些成分在 AD 啮齿动物模型中的促认知作用的证据。