Brain peptide cuts tau damage in Alzheimer mouse models

The protein is called catestatin (CST), a peptide normally released from a larger precursor protein known as chromogranin A. Researchers found that catestatin levels are markedly reduced in the brains of people with Alzheimer’s disease, as well as in two other conditions characterised by tau accumulation: corticobasal degeneration and progressive supranuclear palsy.

Tau is a protein that normally supports the transport system inside healthy neurons. In tauopathies, tau misfolds and clumps into tangles that damage and kill nerve cells. The researchers administered catestatin to mice genetically predisposed to tau pathology (the PS19 model). This led to reduced tau phosphorylation (an early step in tau damage), less neuroinflammation and improved performance in memory tests.

What is the mechanism?

Catestatin appears to act through the adrenergic stress system: it lowered epinephrine (adrenaline) levels in mouse brains and suppressed overactivation of protein kinase A, an enzyme that promotes tau phosphorylation. This reveals a link between chronic adrenergic stress signalling and tau damage that had not been clearly established in prior research.

What are the limitations?

The study, published in Molecular Therapy, was conducted exclusively in mice and cultured brain tissue. Mouse models of Alzheimer’s have historically been poor predictors of what works in humans. The researchers note this themselves: catestatin reduces tau pathology in mice, but does not eliminate it. No curative effect has been demonstrated. Clinical testing in humans has not yet been conducted. The finding is preliminary, but from a longevity perspective it offers an intriguing new mechanism: a naturally occurring peptide that links stress signalling to tau damage in the aging brain.

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