NAD⁺ supplementation normalizes key Alzheimer's features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency.

ABSTRACT: Emerging findings suggest that compromised cellular bioenergetics and DNA repair contribute to the pathogenesis of Alzheimer's disease (AD), but their role in disease-defining pathology is unclear. We developed a DNA repair-deficient 3xTgAD/Polβ^+/- mouse that exacerbates major features of human AD including phosphorylated Tau (pTau) pathologies, synaptic dysfunction, neuronal death, and cognitive impairment. Here we report that 3xTgAD/Polβ^+/- mice have a reduced cerebral NAD⁺/NADH ratio indicating impaired cerebral energy metabolism, which is normalized by nicotinamide riboside (NR) treatment. NR lessened pTau pathology in both 3xTgAD and 3xTgAD/Polβ^+/- mice but had no impact on amyloid β peptide (Aβ) accumulation. NR-treated 3xTgAD/Polβ^+/-<

SUBMITTER: Hou Y 

PROVIDER: S-EPMC5828618 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature