打破百年认知！这种药物能够恢复大脑NAD+稳态，逆转晚期阿尔茨海默病

Core Viewpoint - The article discusses the potential for reversing advanced Alzheimer's disease through the restoration of NAD+ homeostasis, challenging the long-held belief that the disease is irreversible [2][10]. Group 1: Alzheimer's Disease Overview - Over 50 million people worldwide are currently affected by Alzheimer's disease, with projections indicating this number will exceed 150 million by 2050 [1]. - Current treatments primarily target beta-amyloid proteins or provide symptomatic relief, with limited effectiveness [1]. Group 2: Research Breakthroughs - A study published by researchers at Case Western Reserve University demonstrated that the drug P7C3-A20 can restore NAD+ homeostasis, successfully reversing advanced Alzheimer's disease in mice [2][10]. - The research indicates that even late-stage Alzheimer's may be reversible by enhancing the brain's resilience [2][10]. Group 3: Mechanism of Action - NAD+ is a crucial molecule for cellular energy metabolism, involved in energy production, DNA repair, and antioxidant defense [5]. - The study found that NAD+ levels significantly decline as Alzheimer's disease progresses, correlating directly with the severity of the disease [5]. Group 4: Effects of P7C3-A20 - P7C3-A20 treatment not only halted disease progression in late-stage Alzheimer's mouse models but also achieved comprehensive reversal of cognitive deficits [7]. - Post-treatment, animals showed normal performance in memory and learning tests, reduced tau protein phosphorylation, decreased blood-brain barrier damage, and diminished oxidative stress [8]. Group 5: Human Brain Evidence - Analysis of human brain samples revealed a close relationship between NAD+ homeostasis imbalance and the severity of Alzheimer's disease [9]. - Individuals with Alzheimer's pathology but normal cognition (NDAN) exhibited maintained NAD+ homeostasis, suggesting a protective mechanism [9]. Group 6: Future Directions - The study's breakthroughs include the first demonstration that late-stage Alzheimer's-like pathology can be reversed, the identification of NAD+ homeostasis as a central mechanism in disease progression, and the discovery of potential therapeutic targets in the human brain [10][14]. - Future plans involve preclinical safety and efficacy assessments to lay the groundwork for human clinical trials, potentially offering a new treatment direction for Alzheimer's disease [14].