biostudies-literatureMietelska-Porowska ANational Science Center4744https://www.ebi.ac.uk/biostudies/studies/S-EPMC9102094biostudies-literatureUnknown23(9)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 iInternational journal of molecular sciencesInduction of Brain Insulin Resistance and Alzheimer's Molecular Changes by Western Diet.PMC9102094No. UMO-2014/15/D/NZ4/04361Want ADomanska JWojda UMietelska-Porowska AWieckowska-Gacek AChutoranski DKoperski MfalseInduction of Brain Insulin Resistance and Alzheimer's Molecular Changes by Western Diet.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 i2022-01-01T00:00:00Z2022 Apr2025-04-18T14:31:31.142Z2025-02-19T00:56:24.304ZS-EPMC91020943556313510.3390/ijms23094744