Gene transfer of human Apoe isoforms results in differential modulation of amyloid deposition and neurotoxicity in mouse brain.

ABSTRACT: Inheritance of the ε4 allele of apolipoprotein E (APOE) is the strongest genetic risk factor associated with the sporadic form of Alzheimer's disease (AD), whereas the rare APOE ε2 allele has the opposite effect. However, the mechanisms whereby APOE confers risk and protection remain uncertain. We used a gene transfer approach to bathe the cortex of amyloid plaque-bearing transgenic mice with virally expressed human APOE. We monitored amyloid-β (Aβ) with multiphoton imaging, in vivo microdialysis, and postmortem array tomography to study the kinetics of human APOE-mediated changes in Aβ-related neurotoxicity in a mouse model of AD. We observed that human APOE4 increased the concentrations of oligomeric Aβ within the interstitial fluid and exacerbated plaque deposition; the converse occurre

SUBMITTER: Hudry E 

PROVIDER: S-EPMC4334150 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature