High-Fat Diet-Induced Diabetic Conditions Exacerbate Cognitive Impairment in a Mouse Model of Alzheimer’s Disease Via a Specific Tau Phosphorylation Pattern - 21/11/24
, T. Nakajima 3, A. Oyama 2, 3, H. Takeshita 3, K. Miki 1, Y. Takami 3, Y. Takeya 3, 4, M. Shimamura 5, H. Rakugi 3, Ryuichi Morishita 1, ⁎
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Abstract |
Background |
Epidemiological evidence has demonstrated a clear association between diabetes mellitus and increased risk of Alzheimer’s disease (AD). Cerebral accumulation of phosphorylated tau aggregates, a cardinal neuropathological feature of AD, is associated with neurodegeneration and cognitive decline. Clinical and experimental studies indicate that diabetes mellitus affects the development of tau pathology; however, the underlying molecular mechanisms remain unknown.
Objective |
In the present study, we used a unique diabetic AD mouse model to investigate the changes in tau phosphorylation patterns occurring in the diabetic brain.
Design |
Tau-transgenic mice were fed a high-fat diet (n = 24) to model diabetes mellitus. These mice developed prominent obesity, severe insulin resistance, and mild hyperglycemia, which led to early-onset neurodegeneration and behavioral impairment associated with the accumulation of hyperphosphorylated tau aggregates.
Results |
Comprehensive phosphoproteomic analysis revealed a unique tau phosphorylation signature in the brains of mice with diabetic AD. Bioinformatic analysis of the phosphoproteomics data revealed putative tau-related kinases and cell signaling pathways involved in the interaction between diabetes mellitus and AD.
Conclusion |
These findings offer potential novel targets that can be used to develop tau-based therapies and biomarkers for use in AD.
Il testo completo di questo articolo è disponibile in PDF.Key words : Alzheimer’s disease, dementia, diabetes mellitus, tau, post-translational modification
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Vol 11 - N° 1
P. 138-148 - Gennaio 2024 Ritorno al numero
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