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Publication : Detrimental effects of diet-induced obesity on τ pathology are independent of insulin resistance in τ transgenic mice.

First Author  Leboucher A Year  2013
Journal  Diabetes Volume  62
Issue  5 Pages  1681-8
PubMed ID  23250356 Mgi Jnum  J:208588
Mgi Id  MGI:5563738 Doi  10.2337/db12-0866
Citation  Leboucher A, et al. (2013) Detrimental effects of diet-induced obesity on tau pathology are independent of insulin resistance in tau transgenic mice. Diabetes 62(5):1681-8
abstractText  The tau pathology found in Alzheimer disease (AD) is crucial in cognitive decline. Midlife development of obesity, a major risk factor of insulin resistance and type 2 diabetes, increases the risk of dementia and AD later in life. The impact of obesity on AD risk has been suggested to be related to central insulin resistance, secondary to peripheral insulin resistance. The effects of diet-induced obesity (DIO) on tau pathology remain unknown. In this study, we evaluated effects of a high-fat diet, given at an early pathological stage, in the THY-Tau22 transgenic mouse model of progressive AD-like tau pathology. We found that early and progressive obesity potentiated spatial learning deficits as well as hippocampal tau pathology at a later stage. Surprisingly, THY-Tau22 mice did not exhibit peripheral insulin resistance. Further, pathological worsening occurred while hippocampal insulin signaling was upregulated. Together, our data demonstrate that DIO worsens tau phosphorylation and learning abilities in tau transgenic mice independently from peripheral/central insulin resistance.
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