432.11 - Effects of Microglia APOE Expression on Tau Pathology

Samantha Baker (Juniata College), Na Wang (Mayo Clinic Graduate School of Biomedical Sciences), Guojun Bu (Mayo Clinic Graduate School of Biomedical Sciences), Chia-Chen Liu (Mayo Clinic Graduate School of Biomedical Sciences)

Apolipoprotein E (APOE) is a lipid transporter involved in neural cholesterol metabolism. Highly expressed in astrocytes and microglia, APOE4, one of the three isoforms of the transporter, is a strong genetic risk factor for Alzheimer’s disease, while APOE3 is considered moderate risk and APOE2 protective. Despite recent advances in Alzheimer’s disease research, the exact mechanism by which  APOE4 influences the progression of the disease has yet to be determined. One hallmark pathological feature of Alzheimer’s disease is the accumulation of hyperphosphorylated tau protein in the brain. To investigate the role of APOE isoform expression in the accumulation of hyperphosphorylated tau protein, a microglia-specific cre- recombinase-mediated APOE inducible mouse model was used. Phosphorylated-tau accumulation, microglia activation, and neurodegeneration of the hippocampus and piriform cortex upon specific expression of APOE3 were quantified. APOE3 expressing mice had exacerbated neurodegeneration and tau accumulation in the hippocampus. Additionally, it appeared that APOE3 expressing mice had increased microglial activation. Thus, APOE expression may be involved in the activation of microglia in Alzheimer’s disease, eliciting an overactive immune response that accelerates disease progression.

Support or Funding Information

National Institutes of Health RO1 Grant

R01 AG62110

lt;pgt;National Institutes of Health RO1 Grantlt;/pgt;lt;pgt;R01amp;nbsp;AG62110lt;/pgt;