G. Basurto-Islas, YC. Tung, CL. Dai, K. Iqbal and CX. Gong (2024). Diabetic Ketoacidosis Induces Tau Hyperphosphorylation in Rat Brain. Journal of Alzheimer's disease reports, 8(1), 615-626. https://doi.org/10.3233/ADR-240040

PubMed 38746631

[Abstract]
BACKGROUND: Diabetes mellitus (DM) increases the risk for cognitive impairment and Alzheimer's disease (AD). Diabetic ketoacidosis (DKA), a serious complication of DM, may also cause brain damage and further AD, but the underlying molecular mechanisms remain unclear.

OBJECTIVE: Our objective was to understand how DKA can promote neurodegeneration in AD.

METHODS: We induced DKA in rats through intraperitoneal injection of streptozotocin, followed by starvation for 48 hours and investigated AD-related brain alterations focusing on tau phosphorylation.

RESULTS: We found that DKA induced hyperphosphorylation of tau protein at multiple sites associated with AD. Studies of tau kinases and phosphatases suggest that the DKA-induced hyperphosphorylation of tau was mainly mediated through activation of c-Jun N-terminal kinase and downregulation of protein phosphatase 2A. Disruption of the mTOR-AKT (the mechanistic target of rapamycin-protein kinase B) signaling pathway and increased levels of synaptic proteins were also observed in the brains of rats with DKA.

CONCLUSIONS: These results shed some light on the mechanisms by which DKA may increase the risk for AD.