High cholesterol diet induces tau hyperphosphorylation in apolipoprotein E deficient mice

Area of Science:

• Neuroscience
• Genetics
• Biochemistry

Background:

• Apolipoprotein E (apoE) plays a critical role in lipid metabolism and brain health.
• Aberrant tau phosphorylation is a hallmark of neurodegenerative tauopathies, including Alzheimer's disease.
• Dietary factors, such as high cholesterol, may influence neurodegenerative processes.

Purpose of the Study:

• To investigate the combined effects of high cholesterol (HC) intake and reduced apolipoprotein E (apoE) activity on tau phosphorylation.
• To examine the impact on major tau kinases and phosphatases in the brain.
• To explore the potential interaction between dietary and genetic factors in tauopathy development.

Main Methods:

• Analysis of tau phosphorylation, tau kinases, and tau phosphatases in wild-type and apoE-knockout (apoEKO) mouse brains.
• Administration of a high cholesterol (HC) diet to assess its effects.

Main Results:

• A high cholesterol (HC) diet significantly induced intraneuronal accumulation of hyperphosphorylated tau in apoE-knockout (apoEKO) mice.
• The HC diet upregulated several tau kinases but did not affect tau phosphatases in apoEKO mice.
• These findings indicate a potent interaction between dietary cholesterol and genetic apoE deficiency in promoting tau pathology.

Conclusions:

• Dietary and genetic factors interact in the pathogenesis of tauopathies.
• Reduced apolipoprotein E (apoE) activity, combined with high cholesterol intake, promotes tau hyperphosphorylation.
• These findings may have implications for understanding human tauopathies, considering the potential functional impact of the apoE4 isoform.