The ε4 allele of Apolipoprotein E (APOE) is the greatest genetic risk factor for Alzheimer’s disease (AD). In the United States, AD is the most common neurodegenerative dementia and is the 6th leading cause of death (Alzheimer’s Association, 2019). AD is characterized pathologically by the deposition of amyloid β (Aβ) peptides in extracellular plaques and hyperphosphorylated tau protein in intracellular neurofibrillary tangles (NFTs). Clinically, AD is characterized by progressive cognitive impairment. Although there is a large body of evidence demonstrating that different APOE alleles alter amyloid β clearance and thus modify AD pathology, the effect of APOE isoforms on tau pathology is unclear. APOE has three major alleles: ε2, ε3, and ε4. My lab proposes to test the hypothesis that different APOE alleles will influence the development of tau pathology in a mouse model of tauopathy.