What peer‑reviewed research currently shows the most promise for slowing or reversing Alzheimer’s disease?
Executive summary
Recent peer‑reviewed work highlights two promising, but very different, paths: restoring brain cellular energy (NAD+ homeostasis) reversed advanced Alzheimer’s‑like pathology and cognition in multiple mouse models using the compound P7C3‑A20 (Cell Reports Medicine), and computational drug‑repurposing has identified existing cancer drugs that reverse Alzheimer’s gene‑expression signatures and ameliorate disease in models (UCSF) — both offer strong preclinical signals but remain unproven in humans [1] [2].
1. The most direct, peer‑reviewed reversal claim: NAD+ restoration in mice
A December 2025 Cell Reports Medicine paper from Chaubey et al. reports that severe loss of the central cellular energy molecule NAD+ is a driver of Alzheimer’s pathology in human tissue and mouse models, and that pharmacologic restoration of NAD+ balance with P7C3‑A20 prevented disease onset and reversed advanced pathology and cognitive deficits in two distinct Alzheimer’s mouse lines [1] [3]. Multiple institutional press releases and news stories amplify that the intervention normalized biomarkers including phosphorylated tau‑217 in mice and produced full functional recovery in those models [4] [3] [5]. The study is important because it identifies a mechanistic node — brain energy resilience — that is targetable across cell types, not just amyloid or tau, and it is peer‑reviewed [1].
2. Repurposing existing drugs: cancer agents and gene‑signature reversal
Independent work from UCSF/Gladstone used single‑cell human brain gene‑expression signatures to screen drug databases and found two cancer drugs that reverse Alzheimer’s transcriptional changes and improved outcomes in a severe disease model, illustrating a complementary strategy of repurposing approved compounds that modulate pathways altered in human brains [2]. This approach reduces early safety uncertainty because the drugs are already characterized in humans, but success in cellular or animal models does not guarantee clinical benefit for Alzheimer’s, given differences in dosing, blood–brain barrier penetration, and disease complexity [2].
3. Why mouse success is necessary but not sufficient — critical caveats
Experts caution that rodent models do not fully recapitulate human Alzheimer’s: mice can model amyloid or tau pathology but do not naturally develop Alzheimer’s as humans do, and many therapies that worked in rodents failed in clinical trials, a history that tempers enthusiasm for preclinical reversals [6]. Several outlets explicitly note the limitation that results to date are in animal models and human tissue analyses, and that translation requires clinical studies to establish safety, dosing, and meaningful cognitive benefit in people [7] [8].
4. How this work differs from, and complements, antibody and symptomatic approaches
Unlike amyloid‑targeting antibodies that aim to remove plaques and have delivered modest clinical benefit at best, NAD+‑focused and transcriptional‑signature approaches target core cellular resilience and multi‑cell‑type dysfunction, potentially repairing damage rather than only slowing accumulation of pathology; commentators note, however, that current antibody therapies themselves are controversial regarding clinical efficacy [6] [1]. The new strategies are presented by authors and institutions as paradigm‑shifting, a message amplified by university press releases and popular media — an implicit agenda to encourage clinical translation and funding, which readers should note when weighing headlines [4] [5].
5. Where the field must go next: clinical testing, biomarkers and caution
Authors and coverage uniformly call for clinical trials and deeper mechanistic work — including identifying which aspects of brain energy balance are critical, confirming biomarkers in humans, and testing safety because NAD+ modulation can interact with cancer biology and other pathways — and stress that complementary lifestyle measures remain proven ways to support brain health while therapeutics advance [9] [6] [7]. In short, peer‑reviewed preclinical studies identifying NAD+ restoration (P7C3‑A20) and drug‑repurposing candidates (UCSF) are the most promising leads today, but they are not evidence that Alzheimer’s can yet be reversed in people; rigorous human trials are the essential next step [1] [2] [6].