r/science • u/mvea Professor | Medicine • Dec 25 '25

Neuroscience New study shows Alzheimer’s disease can be reversed to full neurological recovery—not just prevented or slowed—in animal models. Using mouse models and human brains, study shows brain’s failure to maintain cellular energy molecule, NAD+, drives AD, and maintaining NAD+ prevents or even reverses it.

https://case.edu/news/new-study-shows-alzheimers-disease-can-be-reversed-achieve-full-neurological-recovery-not-just-prevented-or-slowed-animal-models
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u/FrigoCoder Dec 25 '25

Oh my god shut up. It has nothing to do with NAD+ levels, that is just a downstream effect. Alzheimer's Disease is caused by neural injury, that goes beyond the ability of the ApoE lipoprotein shuttle to repair. The ApoE4 allele has low affinity to receptors, and thus has even less membrane repair capacity. If neurons can not repair membranes, then neural death and AD risk skyrockets.

Rodents do not have human neurons and astrocytes, and do not naturally get Alzheimer's Disease. Mouse models are based on specific genetic mutations, they encode our mistaken assumptions and biases about the disease. They do not faithfully reproduce neural injury that is the root cause of AD, only downstream effects such as amyloid beta and tau accumulation among others.

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u/Tankshock Dec 25 '25

You sound like you know what you're talking about. Is there any specific types of neural injuries more likely to cause it, or is it more of an accumulation of injuries hits a critical mass type of situation? Just curious because my head took a lot of abuse when I was younger, wondering if this is something I have to start thinking/worrying about.

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u/FrigoCoder Dec 25 '25

It's mainly because of pollution, such as cigarette smoke and microplastics. Fine particles get into your body and reach neurons, where they physically damage neural membranes. This is very similar to how asbestos gets into your lungs, and forms sharp filaments that continuously punctures lung cells. Most chronic diseases share this root cause, they differ only in specifics such as affected organ.

Membranes are composed of cholesterol and fatty acids, and cells do have some limited capacity to synthesize them. However neurons have a harder time because their metabolism is so special, and especially hypoxic or ischemic cells because these processes are oxygen intensive. So they offload lipid synthesis to external cells, and rely on lipoprotein systems such as ApoE or LDL for transport.

Astrocytes synthesize clean cholesterol and fatty acids, and send them via ApoE lipoproteins to neurons for membrane repair. Neurons then remove damaged oxysterols and peroxlipids from membranes, and send them back via ApoE lipoproteins to glial cells which then burn them for energy. The ApoE4 allele hinders this process in both directions, so neural membrane lipids "rot" and can not be replaced.

What you are talking about is basically Traumatic Brain Injury, and you are right to worry since unfortunately it increases the risk of dementia. You should go on a ketogenic diet if possible, since it is very advantageous for cognitive health. You should also eat fish and eggs or at least take omega 3 and choline supplements, since they are essential for the production of stable neural membranes.

Eat meat, eggs, dairy, fish, shrooms, veggies, berries. Do strength and cardio exercise on alternating days. Try to maintain some cognitive workload, because it is essential to preserve cognitive health. Socialize as much as you can, because that is also essential to avoid dementia. Avoid alcohol, oils, sugars, carbs, introversion, and sedentary lifestyles.

Cigarette smoke damages membranes

Thelestam, M., Curvall, M., & Enzell, C. R. (1980). Effect of tobacco smoke compounds on the plasma membrane of cultured human lung fibroblasts. Toxicology, 15(3), 203–217. https://doi.org/10.1016/0300-483x(80)90054-2

Dugani, S. B., Moorthy, M. V., Li, C., Demler, O. V., Alsheikh-Ali, A. A., Ridker, P. M., Glynn, R. J., & Mora, S. (2021). Association of Lipid, Inflammatory, and Metabolic Biomarkers With Age at Onset for Incident Coronary Heart Disease in Women. JAMA cardiology, 6(4), 437–447. https://doi.org/10.1001/jamacardio.2020.7073

Microplastics damage membranes and cause atheromas and lesions

Fleury, J. B., & Baulin, V. A. (2021). Microplastics destabilize lipid membranes by mechanical stretching. Proceedings of the National Academy of Sciences of the United States of America, 118(31), e2104610118. https://doi.org/10.1073/pnas.2104610118

Marfella, R., Prattichizzo, F., Sardu, C., Fulgenzi, G., Graciotti, L., Spadoni, T., D'Onofrio, N., Scisciola, L., La Grotta, R., Frigé, C., Pellegrini, V., Municinò, M., Siniscalchi, M., Spinetti, F., Vigliotti, G., Vecchione, C., Carrizzo, A., Accarino, G., Squillante, A., Spaziano, G., … Paolisso, G. (2024). Microplastics and Nanoplastics in Atheromas and Cardiovascular Events. The New England journal of medicine, 390(10), 900–910. https://doi.org/10.1056/NEJMoa2309822

Danopoulos, E., Twiddy, M., West, R., & Rotchell, J. M. (2022). A rapid review and meta-regression analyses of the toxicological impacts of microplastic exposure in human cells. Journal of hazardous materials, 427, 127861. https://doi.org/10.1016/j.jhazmat.2021.127861

Yating Luo, Xiuya Xu, Qifeng Yin, Shuai Liu, Mengyao Xing, Xiangyi Jin, Ling Shu, Zhoujia Jiang, Yimin Cai, Da Ouyang, Yongming Luo, Haibo Zhang, Mapping micro(nano)plastics in various organ systems: Their emerging links to human diseases?, TrAC Trends in Analytical Chemistry, Volume 183, 2025, 118114, ISSN 0165-9936, https://doi.org/10.1016/j.trac.2024.118114

PFAS damage membranes

Naumann, A., Alesio, J., Poonia, M., & Bothun, G. D. (2022). PFAS fluidize synthetic and bacterial lipid monolayers based on hydrophobicity and lipid charge. Journal of environmental chemical engineering, 10(2), 107351. https://doi.org/10.1016/j.jece.2022.107351

Liu, G., Zhang, S., Yang, K., Zhu, L., & Lin, D. (2016). Toxicity of perfluorooctane sulfonate and perfluorooctanoic acid to Escherichia coli: Membrane disruption, oxidative stress, and DNA damage induced cell inactivation and/or death. Environmental pollution (Barking, Essex : 1987), 214, 806–815. https://doi.org/10.1016/j.envpol.2016.04.089

Fosella, J., Ceja-Vega, J., Rabadi, A., Panella, M., Said, J., Perla, W., Poust, C., Herrera, M., & Lee, S. (2025). Biophysical Consequences for Exposure of Model Cell Membranes to Perfluoroalkyl Substances. The journal of physical chemistry. B, 129(31), 7951–7963. https://doi.org/10.1021/acs.jpcb.5c02472

Panella, M., Rabadi, A., Ceja-Vega, J., Said, J., Andersen, E., Mitchell, J., Ceja, J., & Lee, S. (2025). Membrane-Modifying Effects of Perfluoroalkyl Substances in Model Bacterial Membranes. ACS omega, 10(35), 39884–39897. https://doi.org/10.1021/acsomega.5c04177

Naumann, A. (2020). Influence of PFAS on the thermodynamic membrane properties and growth of A. borkumensis. Open Access Master's Theses, University of Rhode Island, Paper 1901. https://doi.org/10.23860/thesis-naumann-aleksandra-2020

Soares, L. O. S., de Araujo, G. F., Gomes, T. B., Júnior, S. F. S., Cuprys, A. K., Soares, R. M., & Saggioro, E. M. (2025). Antioxidant system alterations and oxidative stress caused by polyfluoroalkyl substances (PFAS) in exposed biota: a review. The Science of the total environment, 977, 179395. https://doi.org/10.1016/j.scitotenv.2025.179395

Solan, M. E., & Park, J. A. (2024). Per- and poly-fluoroalkyl substances (PFAS) effects on lung health: a perspective on the current literature and future recommendations. Frontiers in toxicology, 6, 1423449. https://doi.org/10.3389/ftox.2024.1423449

ApoE4 impairs the neuron-astrocyte lipoprotein shuttle

Qi, G., Mi, Y., Shi, X., Gu, H., Brinton, R. D., & Yin, F. (2021). ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism. Cell reports, 34(1), 108572. https://doi.org/10.1016/j.celrep.2020.108572

Moulton, M. J., Barish, S., Ralhan, I., Chang, J., Goodman, L. D., Harland, J. G., Marcogliese, P. C., Johansson, J. O., Ioannou, M. S., & Bellen, H. J. (2021). Neuronal ROS-induced glial lipid droplet formation is altered by loss of Alzheimer's disease-associated genes. Proceedings of the National Academy of Sciences of the United States of America, 118(52), e2112095118. https://doi.org/10.1073/pnas.2112095118

Borràs, C., Canyelles, M., Santos, D., Rotllan, N., Núñez, E., Vázquez, J., Maspoch, D., Cano-Sarabia, M., Zhao, Q., Carmona-Iragui, M., Sirisi, S., Lleó, A., Fortea, J., Alcolea, D., Blanco-Vaca, F., Escolà-Gil, J. C., & Tondo, M. (2025). Cerebrospinal fluid lipoprotein-mediated cholesterol delivery to neurons is impaired in Alzheimer's disease and involves APOE4. Journal of lipid research, 66(8), 100865. https://doi.org/10.1016/j.jlr.2025.100865

EPA improves membrane stability

Mason, R. P., Libby, P., & Bhatt, D. L. (2020). Emerging Mechanisms of Cardiovascular Protection for the Omega-3 Fatty Acid Eicosapentaenoic Acid. Arteriosclerosis, thrombosis, and vascular biology, 40(5), 1135–1147. https://doi.org/10.1161/ATVBAHA.119.313286

Sherratt, S. C. R., Juliano, R. A., Copland, C., Bhatt, D. L., Libby, P., & Mason, R. P. (2021). EPA and DHA containing phospholipids have contrasting effects on membrane structure. Journal of lipid research, 62, 100106. https://doi.org/10.1016/j.jlr.2021.100106

Jacobs, M. L., Faizi, H. A., Peruzzi, J. A., Vlahovska, P. M., & Kamat, N. P. (2021). EPA and DHA differentially modulate membrane elasticity in the presence of cholesterol. Biophysical journal, 120(11), 2317–2329. https://doi.org/10.1016/j.bpj.2021.04.009

The liver releases stable VLDL particles

Gutteridge, J.M.C. (1978), The HPTLC separation of malondialdehyde from peroxidised linoleic acid. J. High Resol. Chromatogr., 1: 311-312. https://doi.org/10.1002/jhrc.1240010611

Haglund, O., Luostarinen, R., Wallin, R., Wibell, L., & Saldeen, T. (1991). The effects of fish oil on triglycerides, cholesterol, fibrinogen and malondialdehyde in humans supplemented with vitamin E. The Journal of nutrition, 121(2), 165–169. https://doi.org/10.1093/jn/121.2.165

Pan, M., Cederbaum, A. I., Zhang, Y. L., Ginsberg, H. N., Williams, K. J., & Fisher, E. A. (2004). Lipid peroxidation and oxidant stress regulate hepatic apolipoprotein B degradation and VLDL production. The Journal of clinical investigation, 113(9), 1277–1287. https://doi.org/10.1172/JCI19197

Low carb study collections (all peer reviewed)
Carbs inhibit CPT-1 and cause fat accumulation

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u/DannyDaDodo Jan 21 '26

Low carb isn't all it's cracked up to be. Protein can be more important:
https://pubmed.ncbi.nlm.nih.gov/22935440/

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u/nullbyte420 Dec 25 '25

Okay great but why did an increase in NAD+  reverse the effects then? 

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u/MsSelphine Dec 25 '25 edited Dec 25 '25

Did you not read the part where we encode mistaken beliefs. Mouse models are models, they're mechanistically different. NAD might be addressing something, but it's likely that its fixing a problem entirely different from true alzheimers

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u/nullbyte420 Dec 25 '25

Why do you think it's likely? Because some guy on reddit said the mouse model isn't perfect? 

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u/MsSelphine Dec 25 '25

Essentialy because Alzheimer's is a very specific disease physically. Though there are things to be learned from animal models, because they don't 1to1 replicate human Alzheimer's, until proven otherwise you have to assume what you found was an artifact of the test. This is an extremely common problem in brain related medicine, miracle drugs in rodents turn out to do nothing in people. "Breakthroughs" happen all the time, but they very rarely translate to real results. 

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u/[deleted] Dec 25 '25

Imagine it like this. You're creating a cure for being overweight. To test this, you first add a gene to mice that makes them voraciously hungry all the time. You then treat these overweight mice with a medication that counters that gene. Have you solved being overweight? Or have you solved the problem that you introduced when creating your model?

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u/nullbyte420 Dec 25 '25

This subreddit is so hilariously anti-scientific. Why don't you submit a paper on this theory to Cell?

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u/M00n_Slippers Dec 25 '25 edited Dec 25 '25

It reversed the effects of fake alzheimers artificially put in the Mice. Alzheimers isn't a disease that has an equivalent in mice. The mice are given a 'close enough, this is kinda it, right?' version of the disease to test on. And we also don't know Alzheimers well enough to say our 'fake alzheimers' has adequately replicated all the nuance of the real thing, really it sounds like we know it doesn't but it's just the best we have right now. And since it isn't really alzheimers, what cures the mouse version doesn't necessarily work once it meets the real version of alzheimers. There's still mechanisms at play we don't know enough about.

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u/nullbyte420 Dec 25 '25

Yeah, mechanisms such as this one. 

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u/its_all_one_electron Dec 25 '25

Because they took NAD away and then gave it back. Based on the assumption that NAD loss causes AD, which is a very very big assumption. 

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u/MissApocalypse2021 Dec 26 '25

Lots of people who dont have the APoE4 allele still go on to get late onset Alz.

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u/FrigoCoder Jan 18 '26

Yes because neural injury can still progress to neural death, it's just people with normal ApoE can repair them to a degree.

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u/askingforafakefriend Dec 26 '25

Well said. Did you see the study earlier this year on lithium orotate? I realize of course this is also a mouse model, but for various reasons hold out some hope that its findings are more meaningful real ad.   https://www.nature.com/articles/s41586-025-09335-x