Induction of Brain Insulin Resistance and Alzheimer’s Molecular Changes by Western Diet

Autor: Anna Mietelska-Porowska, Justyna Domańska, Andrew Want, Angelika Więckowska-Gacek, Dominik Chutorański, Maciej Koperski, Urszula Wojda
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 23, Iss 9, p 4744 (2022)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms23094744
Popis: The term Western diet (WD) describes the consumption of large amounts of highly processed foods, rich in simple sugars and saturated fats. Long-term WD feeding leads to insulin resistance, postulated as a risk factor for Alzheimer’s disease (AD). AD is the main cause of progressive dementia characterized by the deposition of amyloid-β (Aβ) plaques and neurofibrillary tangles consisting of the hyperphosphorylated tau (p-Tau) protein in the brain, starting from the entorhinal cortex and the hippocampus. In this study, we report that WD-derived impairment in insulin signaling induces tau and Aβ brain pathology in wild-type C57BL/6 mice, and that the entorhinal cortex is more sensitive than the hippocampus to the impairment of brain insulin signaling. In the brain areas developing WD-induced insulin resistance, we observed changes in p-Tau(Thr231) localization in neuronal subcellular compartments, indicating progressive tauopathy, and a decrease in amyloid precursor protein levels correlating with the appearance of Aβ peptides. These results suggest that WD promotes the development of AD and may be considered not only a risk factor, but also a modifiable trigger of AD.
Databáze: Directory of Open Access Journals
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