Catestatin ameliorates tauopathy and amyloidogenesis via adrenergic inhibition

Jan 9, 2026bioRxiv : the preprint server for biology

Catestatin may reduce abnormal tau and amyloid buildup by blocking adrenaline signals

AI simplified

Alzheimers & Treatments on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

Significant reductions in Catestatin (CST) levels were found in the hippocampus and cortex of Alzheimer’s disease brains.

CST, a peptide derived from chromogranin A, is linked to Tau pathology.
CST levels were notably lower in the frontal cortex of Corticobasal Degeneration and in the basal ganglia of Progressive Supranuclear Palsy.
Supplementation of CST in neuronal cultures reduced Tau phosphorylation and aggregation.
CST administration in PS19 Tauopathy mice decreased pathological Tau species and improved cognitive function.
CST treatment also reduced amyloid plaque burden and neuroinflammation in 5xFAD mice.
CST appears to decrease epinephrine levels and suppresses hyperactivation of protein kinase A, linking CST deficiency to Tauopathy-associated neurodegeneration.

AI simplified

Neurodegenerative disorders like Alzheimer's disease (AD), Corticobasal Degeneration (CBD), and Progressive Supranuclear Palsy (PSP) are characterized by Tau aggregation, synaptic dysfunction, neuroinflammation, and progressive cognitive decline. Although metabolic dysregulation and neuropeptide imbalance have been linked to these disorders, the functional consequences of such imbalance and its potential for therapeutic reversal remain poorly understood. Our previous work identified chromogranin A (CgA), which encodes a pro-hormone for several metabolic peptides, as a key regulator of Tau pathology. Here, we investigate Catestatin (CST), a CgA-derived peptide that is a potent inhibitor of catecholamine release and has been shown to increase insulin sensitivity and lower peripheral blood pressure. We report significant reductions in CST levels in the hippocampus and cortex of AD brains, as well as in the frontal cortex of CBD and the basal ganglia of PSP. Supplementing CST in cortical neuronal cultures and organotypic slice cultures (OTSC) decreased Tau phosphorylation and aggregation., CST administration in PS19 Tauopathy mice reduced pathological Tau species, attenuated gliosis, and improved cognitive function. CST treatment also lowered amyloid plaque burden and neuroinflammation in 5xFAD mice. Mechanistically, CST decreased epinephrine (EPI) levels in both PS19 and 5xFAD mice and suppressed downstream protein kinase A (PKA) hyperactivation in PS19 and OTSC. These findings reveal a previously unrecognized neuropeptidergic mechanism linking CST deficiency to elevated adrenergic receptor (ADR)-EPI-PKA stress signaling and Tauopathy-driven neurodegeneration, suggesting CST replacement as a promising therapeutic approach. In vivo

Full Text

Full text is available at the source.

View full text ↗

Catestatin ameliorates tauopathy and amyloidogenesis via adrenergic inhibition

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the alzheimers & treatments brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the alzheimers & treatments brief