Pharmacologic reversal of advanced Alzheimer's disease in mice and identification of potential therapeutic nodes in human brain.

ABSTRACT: Alzheimer's disease (AD) is traditionally considered irreversible. Here, however, we provide proof of principle for therapeutic reversibility of advanced AD. In advanced disease amyloid-driven 5xFAD mice, treatment with P7C3-A20, which restores nicotinamide adenine dinucleotide (NAD⁺) homeostasis, reverses tau phosphorylation, blood-brain barrier deterioration, oxidative stress, DNA damage, and neuroinflammation and enhances hippocampal neurogenesis and synaptic plasticity, resulting in full cognitive recovery and reduction of plasma levels of the clinical AD biomarker p-tau217. P7C3-A20 also reverses advanced disease in tau-driven PS19 mice and protects human brain microvascular endothelial cells from oxidative stress. In humans and mice, pathology severity correlates with disr

SUBMITTER: Chaubey K 

PROVIDER: S-EPMC12866132 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature