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

• Published in: International journal of molecular sciences Vol. 23; no. 9; p. 4744
• Main Authors: Mietelska-Porowska, Anna, Domańska, Justyna, Want, Andrew, Więckowska-Gacek, Angelika, Chutorański, Dominik, Koperski, Maciej, Wojda, Urszula
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25-04-2022; MDPI
• Subjects: Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - metabolism; Amyloid precursor protein; Animals; Brain - metabolism; brain insulin resistance; Dementia disorders; Diet, Western - adverse effects; Food processing; Hippocampus; Impairment; Insulin; Insulin - metabolism; Insulin resistance; Insulin Resistance - physiology; insulin signaling; Kinases; Localization; Mice; Mice, Inbred C57BL; Neurofibrillary tangles; Pathology; Peptides; Plaque, Amyloid - metabolism; Plaques; Proteins; Risk analysis; Risk factors; Sugar; Tau protein; tau Proteins - metabolism; Western diet; β-Amyloid; brain insulin resistance; insulin signaling; Alzheimer’s disease; Western diet
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23094744

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.