Apolipoprotein E Facilitates Amyloid-β Oligomer-Induced Tau Phosphorylation

Area of Science:

• Neuroscience
• Genetics
• Biochemistry

Background:

• Hyperphosphorylated tau is a hallmark of Alzheimer's disease (AD), correlating with cognitive decline.
• APOEɛ4 is the primary genetic risk factor for AD, and its role in tau pathology is implicated.

Purpose of the Study:

• To investigate the role of Apolipoprotein E (ApoE) in tau phosphorylation induced by amyloid-beta oligomers (AβO).
• To explore the potential mechanism involving inflammation in ApoE-mediated tau pathology.

Main Methods:

• Intracerebroventricular injection of AβO into wild-type (WT) and apoE-/- mice.
• In vitro studies using cultured neurons treated with different ApoE isoforms (ɛ2, ɛ3, ɛ4) and AβO.
• Assessment of phosphorylated tau and phosphokinase levels.
• Evaluation of inflammatory responses and the effect of anti-inflammatory treatment.

Main Results:

• WT mice and ApoE-positive neurons showed higher levels of phosphorylated tau and phosphokinases compared to apoE-/- mice and ApoE-deficient neurons after AβO exposure.
• ApoEɛ4 treatment resulted in greater tau phosphorylation than ApoEɛ2 or ApoEɛ3.
• AβO induced significant inflammation in WT mice and ApoE-positive neurons.
• Anti-inflammatory treatment attenuated AβO-induced tau phosphorylation in ApoE-positive neurons.

Conclusions:

• Apolipoprotein E (ApoE) may facilitate AβO-induced tau phosphorylation.
• Inflammation appears to be a key mediator in the process of ApoE-facilitated tau pathology.
• These findings suggest ApoE's role in AD pathogenesis and highlight inflammation as a potential therapeutic target.