High cholesterol diet induces tau hyperphosphorylation in apolipoprotein E deficient mice |
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| Authors: | Rahman Atiqur Akterin Susanne Flores-Morales Amilcar Crisby Milita Kivipelto Miia Schultzberg Marianne Cedazo-Mínguez Angel |
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| Affiliation: | Karolinska Institutet, Neurotec Department, Division of Experimental Geriatrics, Novum, Karolinska University Hospital, SE-14186 Huddinge, Sweden. |
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| Abstract: | We analysed the effects of high cholesterol (HC) intake and reduced apolipoprotein E (apoE) activity on tau phosphorylation and on the activities of the major tau kinases and phosphatases in brains from wild-type and apoE-knockout (apoEKO) mice. We show that HC diet potently induced intraneuronal accumulation of hyperphosphorylated tau in apoEKO mice, as well as upregulation of several tau kinases, without affecting tau phosphatases. Our results suggest an interaction between dietary and genetic factors in the development of tauopathies, which can be relevant in humans, where the apoE4 isoform could have a lack of function as compared to other isoforms. |
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| Keywords: | AD, Alzheimer’s disease apoE, apolipoprotein E apoEKO, apoE-knockout CaMKII, calmodulin-dependent protein kinase II cdk-5, cyclin-dependent protein kinase-5 ERK, extracellular regulatory kinase FTD, frontotemporal dementia GSK-3, glycogen synthase kinase-3 HC, high cholesterol NFTs, neurofibrillary tangles NPC, Niemann-Pick type C disease ND, normal diet PBS, phosphate-buffered saline PKA, protein kinase A PP, protein phosphatase WT, wild-type |
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