Reversing late-stage Alzheimer's

A mouse study that gives me hope

This new study on Alzheimer’s disease reversal gives me hope this holiday season.

Caveat first: It’s a mouse study, and Alzheimer’s studies in mice have traditionally not translated well to humans. But this study uses multiple genetic models of different ways of causing Alzheimer’s in different strains of mice. Plus, the mechanism here is one that makes sense.

Let’s dig into the study:

The researchers used a compound called P7C3-A20 to restore NAD+ levels in the brains of different mouse models of Alzheimer’s. They were able to prevent or reverse behavioral and physiological changes of Alzheimer’s, depending on when the compound was given (mid-life or after the onset of Alzheimer’s). The compound also reversed deterioration of the blood-brain barrier.¹

NAD+ (Nicotinamide Adenine Dinucleotide) is a co-enzyme used in every cell in the body for ATP production in the mitochondria. Its levels naturally decline with age, leading to fatigue and age-related issues.

NAD+ is also a co-substrate for sirtuins, which are proteins that help to regulate DNA repair and cellular metabolism.

The study showed that NAD⁺ dysregulation correlates with the severity of Alzheimer’s disease, and there is more dysregulation in AD brains than is normal for the NAD+ decline found in aging.

Importantly, the study found that “pharmacologically normalizing NAD⁺ homeostasis with P7C3-A20 restores brain resilience and enables recovery from advanced disease across diverse mouse AD models”.

What is this magic compound, P7C3-A20?
It’s a research chemical that has been studied for about 15 years for restoring normal NAD+ metabolism in the brain after TBI, ischemic stroke, Alzheimer’s, or Parkinson’s. It does so without elevating NAD+ above normal levels. ²³

The compound has been tested in mice, rats, and monkeys in an oral form, but I didn’t find any human clinical trials on it. It works by activating nicotinamide phosphoribosyltransferase (NAMPT), which increases intracellular levels of NAD. ⁴

What are the current options today?

Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are currently available as supplements and can increase NAD+ levels. A number of animal studies have shown that NMN or NR holds promise for preventing Alzheimer’s (but not to the extent of P7C3-A20).⁵⁶

A clinical trial in adults with mild cognitive impairments found that multiple supplements, including nicotinamide riboside, NAC, L-serine, and L-carnitine, resulted in cognitive improvements.⁷

What about just nicotinamide (niacin)? A phase IIa clinical trial in older adults with mild cognitive impairment did not show significant results after 48 weeks with nicotinamide supplementation, indicating that it isn’t a lack of dietary niacin.⁸

Conclusion:

The current options of NR and NMN to increase NAD+ seem to help some with Alzheimer’s prevention in early stages, but the compound P7C3-A20 seems to hold more benefits specific to brain function. I’m hopeful that it, or another similar compound that normalizes NAD+ in the brain, will be trialed in humans soon.

1. Chaubey, Kalyani, et al. “Pharmacologic Reversal of Advanced Alzheimer’s Disease in Mice and Identification of Potential Therapeutic Nodes in Human Brain.” Cell Reports Medicine, Dec. 2025, p. 102535. DOI.org (Crossref), https://doi.org/10.1016/j.xcrm.2025.102535.

2. Loris, Zachary B., et al. “The Neuroprotective Compound P7C3-A20 Promotes Neurogenesis and Improves Cognitive Function after Ischemic Stroke.” Experimental Neurology, vol. 290, Apr. 2017, pp. 63–73. ScienceDirect, https://doi.org/10.1016/j.expneurol.2017.01.006.

3. Vázquez-Rosa, Edwin, et al. “P7C3-A20 Treatment One Year after TBI in Mice Repairs the Blood–Brain Barrier, Arrests Chronic Neurodegeneration, and Restores Cognition.” Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 44, Nov. 2020, pp. 27667–75. PubMed Central, https://doi.org/10.1073/pnas.2010430117.

4. Bauman, Melissa D., et al. “Neuroprotective Efficacy of P7C3 Compounds in Primate Hippocampus.” Translational Psychiatry, vol. 8, no. 1, Sept. 2018, p. 202. www.nature.com, https://doi.org/10.1038/s41398-018-0244-1.

5. Ma, Rui-Yin, et al. “Therapeutic Effect of Nicotinamide Mononucleotide on Alzheimer’s Disease through Activating Autophagy and Anti-Oxidative Stress.” Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 178, Sept. 2024, p. 117199. PubMed, https://doi.org/10.1016/j.biopha.2024.117199.

6. Zhao, Xiaodong, et al. “Nicotinamide Mononucleotide Improves the Alzheimer’s Disease by Regulating Intestinal Microbiota.” Biochemical and Biophysical Research Communications, vol. 670, Aug. 2023, pp. 27–35. ScienceDirect, https://doi.org/10.1016/j.bbrc.2023.05.075.

7. Yulug, Burak, et al. “Combined Metabolic Activators Improve Cognitive Functions in Alzheimer’s Disease Patients: A Randomised, Double-Blinded, Placebo-Controlled Phase-II Trial.” Translational Neurodegeneration, vol. 12, no. 1, Jan. 2023, p. 4. PubMed, https://doi.org/10.1186/s40035-023-00336-2.

8. Yulug, Burak, et al. “Combined Metabolic Activators Improve Cognitive Functions in Alzheimer’s Disease Patients: A Randomised, Double-Blinded, Placebo-Controlled Phase-II Trial.” Translational Neurodegeneration, vol. 12, no. 1, Jan. 2023, p. 4. PubMed, https://doi.org/10.1186/s40035-023-00336-2.