Brain insulin response and peripheral metabolic changes in a Tau transgenic mouse model.

Brain insulin response and peripheral metabolic changes in a Tau transgenic mouse model. Neurobiol Dis. 2019 Jan 18;: Authors: Leboucher A, Ahmed T, Caron E, Tailleux A, Raison S, Joly-Amado A, Marciniak E, Carvalho K, Hamdane M, Bantubungi K, Lancel S, Eddarkaoui S, Caillierez R, Vallez E, Staels B, Vieau D, Balschun D, Buee L, Blum D Abstract Accumulation of hyper-phosphorylated and aggregated Tau proteins is a neuropathological hallmark of Alzheimer's Disease (AD) and Tauopathies. AD patient brains also exhibit insulin resistance. Whereas, under normal physiological conditions insulin signaling in the brain mediates plasticity and memory formation, it can also regulate peripheral energy homeostasis. Thus, in AD, brain insulin resistance affects both cognitive and metabolic changes described in these patients. While a role of Aβ oligomers and APOE4 towards the development of brain insulin resistance emerged, contribution of Tau pathology has been largely overlooked. Our recent data demonstrated that one of the physiological function of Tau is to sustain brain insulin signaling. We postulated that under pathological conditions, hyper-phosphorylated/aggregated Tau is likely to lose this function and to favor the development of brain insulin resistance. This hypothesis was substantiated by observations from patient brains with pure Tauopathies. To address the potential link between Tau pathology and brain insulin resistance, we have ...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research