dietary cholesterol and its effect on tau protein a study in apolipoprotein edeficient and p301l human tau mice apolipoprotein e apoe is the major cholesterol transporter in the brain there is epidemiological and experimental evidence for involvement of cholesterol metabolism in the development and progression of alzheimer disease a dietary effect on tau phosphorylation or aggregation or a role of apoe in tau metabolism has been studied experimentally but the data are ambiguous to elucidate the relationship between cholesterol and tau we studied mice expressing p301l mutant human tau but not apoe htauapoe and p301l mice with wildtype apoe htau apoe both genotypes develop neuron cytoskeletal changes similar to those found in alzheimer disease mice were kept on a cholesterolenriched diet or control diet for 15 weeks the numbers of neurons with hyperphosphorylated and conformationally changed tau in the cerebral cortex were assessed by immunohistochemistry and sterol levels were determined highly elevated dietary serum cholesterol levels enhanced ongoing tau pathology in htauapoe mice this effect correlated with elevated brain cholesterol metabolite 27hydroxycholesterol levels apolipoprotein e deficiency promoted significant increases of tau phosphorylation and conformational changes in mice on a control diet in htauapoe mice on the high cholesterol regimen brain oxysterol levels were less than in htauapoe mice and the numbers of neurons with pathologically altered tau were similar to those in htauapoe mice on the highcholesterol diet