Catestatin and Alzheimer's: A Peptide the Body Already Makes Reduced Tau and Amyloid in Mice

Alzheimer's treatment news usually comes with a lot of hope attached, and most of it describes early laboratory work. This study is early laboratory work too, though the biology behind it is unusual enough that I wanted to walk through it. A team at the University of California San Diego reports that catestatin, a small peptide the human body already produces, reduced the two hallmark proteins of Alzheimer's disease in mice [1]. A peptide is a short chain of amino acids, the same building blocks that make up proteins.

Photo: National Cancer Institute / Unsplash

What the catestatin study found

Catestatin is a fragment of a larger protein called chromogranin A, and its best-known job is to restrain the release of adrenaline and related stress hormones [4]. The researchers started by examining brain tissue from people who had died with Alzheimer's disease and two related conditions. Catestatin levels were markedly lower in the memory and thinking regions of the brains with Alzheimer's, and also lower in the affected regions in the other two conditions [1].

Then they tested what happens when catestatin is added back. In brain cells grown in the lab and in slices of brain tissue kept alive in a dish, catestatin reduced the chemical changes and clumping of tau, the protein that forms tangles inside nerve cells [1]. In a mouse model bred to develop tau tangles, catestatin reduced the harmful forms of tau, reduced activation of the brain's support cells, and improved the mice's performance on cognitive tests. In a second mouse model that develops amyloid plaques, it reduced plaque buildup and brain inflammation [1]. Amyloid plaques are clumps of a different protein, beta-amyloid, that build up between nerve cells. In both kinds of mice, catestatin lowered epinephrine (adrenaline) levels, and it reduced the activity of a stress-signaling enzyme inside nerve cells.

These results come from cells, brain slices, and mice, along with measurements in donated human brain tissue. As far as I could find, catestatin has not yet been tested in people with Alzheimer's disease.

What other chromogranin A research has found

The same lab reported in 2025 that removing chromogranin A entirely from tau-prone mice reduced tau clumping, extended their lifespan, and improved their cognition [2]. In that work, adrenaline levels were elevated in the brains of the tau mice, and the researchers described a similar pattern in brain tissue from people with Alzheimer's disease and corticobasal degeneration [2]. Corticobasal degeneration is a rarer brain disease that also involves tau tangles.

In a 2026 study, the same group noted that roughly 20 to 30 percent of older people carry substantial amyloid and tau in their brains yet stay cognitively intact [3]. Their chromogranin A-deficient mice behaved in a similar way, showing Alzheimer's-like changes in brain tissue while keeping their learning and memory [3]. That is one reason researchers are interested in factors that might separate the protein buildup from the memory loss.

Outside the brain, catestatin has mostly been studied in the heart and blood vessels. A 2022 review describes it as a restraint on excessive sympathetic nervous system activity, with clinical studies linking it to high blood pressure, coronary artery disease, and heart failure [4]. The sympathetic nervous system is the branch of the nervous system behind the fight-or-flight response. A 2026 review of catestatin as a heart disease marker cautioned that most of the evidence on how catestatin works comes from animal and laboratory work and that the human studies are small and inconsistent [5].

All of the Alzheimer's findings above come from one research group, and I have not seen an independent replication.

The adrenaline connection, seen from a naturopathic practice

What caught my attention in this paper is the stress-hormone connection. Many of my patients live with a stress response that stays switched on, including those with hyperadrenergic forms of dysautonomia, where adrenaline-type hormones are high. Dysautonomia is a problem with the automatic part of the nervous system that controls things like heart rate and blood pressure. This study does not show that calming that system protects the human brain, and I would not tell anyone it does. It does give me one more reason to take a chronically overactive stress response seriously in its own right, through things like sleep, nervous-system regulation, and blood pressure care, rather than treating it as something to push through.

What you can do about memory while the peptide research continues

Catestatin is still a laboratory finding, and nobody can try it as a treatment yet. These three steps are available to you today.

1. Peptides sold online. If you see a peptide marketed for memory or brain health, talk with your provider before taking it. A product sold that way has usually not been through the testing a medication goes through, and nobody knows what a safe human dose would be.

2. A medication review. In a study of more than 284,000 older adults in England, people with the highest cumulative use of strongly anticholinergic medications had about 50 percent higher odds of a dementia diagnosis [6]. Anticholinergic medications block acetylcholine, a chemical messenger that nerves use, and the group includes some bladder, mood, and seizure medications. That study was observational, so it cannot prove cause, and you should never stop a prescribed medication on your own. A pharmacist or prescriber can go through your full medication list and point out any anticholinergic ones.

3. Memory changes checked early. If you or someone close to you notices changes in memory or thinking, ask a provider for a memory evaluation now instead of waiting to see whether the changes get worse.

References

1. Jati S, Kal S, Munoz-Mayorga D, et al. Catestatin peptide ameliorates tauopathy and amyloidogenesis via adrenergic inhibition. Mol Ther. 2026. PMID 42768750. doi:10.1016/j.ymthe.2026.09.022. Original news coverage (AANP digest): https://thehill.com/policy/healthcare/6110798-natural-human-peptides-alzheimers-treatment-study/

2. Jati S, Munoz-Mayorga D, Shahabi S, et al. Chromogranin A deficiency attenuates tauopathy by altering epinephrine-alpha-adrenergic receptor signaling in PS19 mice. Nat Commun. 2025;16(1):4703. PMID 40393970. doi:10.1038/s41467-025-59682-6

3. Jati S, Taheri S, Kal S, et al. AI guided discovery of a murine model of asymptomatic Alzheimer's disease. Acta Neuropathol Commun. 2026;14(1). PMID 41935326. doi:10.1186/s40478-026-02286-y

4. Zalewska E, Kmieć P, Sworczak K. Role of Catestatin in the Cardiovascular System and Metabolic Disorders. Front Cardiovasc Med. 2022;9:909480. PMID 35665253. doi:10.3389/fcvm.2022.909480

5. Gubareva IV, Gubareva EY, Tokarev SA, Shvan LY. Catestatin as a Marker of Cardiovascular Diseases. Cardiovasc Hematol Disord Drug Targets. 2026. PMID 42411095. doi:10.2174/011871529X447719260514063200

6. Coupland CAC, Hill T, Dening T, Morriss R, Moore M, Hippisley-Cox J. Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study. JAMA Intern Med. 2019;179(8):1084-1093. PMID 31233095. doi:10.1001/jamainternmed.2019.0677 (Yggdrasil abstract library)

This post is for education only and is not medical advice. Please talk with your own healthcare provider about memory concerns and before starting, stopping, or changing any medication or supplement.

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If this resonates with what you're experiencing and you'd like to explore a naturopathic approach, book a consultation with our clinic.