2016
DOI: 10.1016/j.neuroscience.2015.12.011
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Obesity, diabetes, and leptin resistance promote tau pathology in a mouse model of disease

Abstract: Obesity and type 2 diabetes mellitus (T2DM) convey an increased risk for developing dementia. The microtubule associated protein tau is implicated in neurodegenerative disease by undergoing hyperphosphorylation and aggregation, leading to cytotoxicity and neurodegeneration. Enzymes involved in the regulation of tau phosphorylation, such as GSK3β, are tightly associated with pathways found to be dysregulated in T2DM. We have shown previously that leptin resistant mice, which develop obesity and a diabetic pheno… Show more

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Cited by 75 publications
(43 citation statements)
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“…Although db/db mice do not develop neurofibrillary tangles, viral vector-mediated expression of human tau P301 in db/db mice generates more extensive pathology, relative to Wt mice (Platt et al, 2016). While effects in db/db mice have primarily been interpreted as a consequence of leptin receptor insufficiency, db/db mice exhibit widespread physiological disruption that impacts other known regulators of tau phosphorylation, including glucocorticoids and insulin receptor signaling (Doble and Woodgett, 2003; Beck et al, 2009).…”
Section: Discussionmentioning
confidence: 99%
“…Although db/db mice do not develop neurofibrillary tangles, viral vector-mediated expression of human tau P301 in db/db mice generates more extensive pathology, relative to Wt mice (Platt et al, 2016). While effects in db/db mice have primarily been interpreted as a consequence of leptin receptor insufficiency, db/db mice exhibit widespread physiological disruption that impacts other known regulators of tau phosphorylation, including glucocorticoids and insulin receptor signaling (Doble and Woodgett, 2003; Beck et al, 2009).…”
Section: Discussionmentioning
confidence: 99%
“…In rodent models of T2DM, diabetes or hyperinsulinemia alters the tau splice patterns and increases tau phosphorylation (Freude et al, 2005;Jung et al, 2011;Kim et al, 2009). A recent study showed that administration of adeno-associated virus-tau mutant (taup 301L ) to T2DM mice significantly increases tau phosphorylation and the number of neurofibrillary tangles within the hippocampus (Platt et al, 2016). In the present study, we identified 13 differentially expressed protein spots and subsequently identified these proteins in the hippocampal homogenates using DIGE coupled with MALDI-TOF MS to identify possible biomarkers in the hippocampus of T2DM.…”
Section: Discussionmentioning
confidence: 99%
“…Epidemiologic studies suggest that diabetes mellitus (DM), a complex metabolic disorder, is a risk factor for cognitive decline . Long‐term diabetes‐induced cognitive decline is characterized by neuropathological alterations including synapse loss, neuronal apoptosis, tau phosphorylation and advanced glycation end products (AGEs) . Recently, there has been an increasing interest in the notion that activated innate immunity is the critical pathogeneses of diabetes‐related cognitive disorder .…”
Section: Introductionmentioning
confidence: 99%