High cholesterol diet induces tau hyperphosphorylation in apolipoprotein E deficient mice.
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.
Rahman
Atiqur
A
Karolinska Institutet, Neurotec Department, Division of Experimental Geriatrics, Novum, Karolinska University Hospital, SE-14186 Huddinge, Sweden.
Akterin
Susanne
S
Flores-Morales
Amilcar
A
Crisby
Milita
M
Kivipelto
Miia
M
Schultzberg
Marianne
M
Cedazo-Mínguez
Angel
A
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D002540:Cerebral Cortex / Q000378:metabolism; D002784:Cholesterol / Q000008:administration & dosage*; D004032:Diet; D051379:Mice; D018345:Mice, Knockout; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D024801:Tauopathies / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D016875:tau Proteins / Q000378:metabolism*
D001057:Apolipoproteins E; D016875:tau Proteins; D002784:Cholesterol; D017346:Protein Serine-Threonine Kinases; D010744:Phosphoric Monoester Hydrolases