Intracerebral Expression of AAV-APOE4 Is Not Sufficient to Alter Tau Burden in Two Distinct Models of Tauopathy.

Journal Article (Journal Article)

Apolipoprotein E4 (APOE4) is the major genetic risk factor for sporadic Alzheimer's disease (AD), which is characterized by amyloid β (Aβ) plaques and tau tangles. Though the role of APOE4 in Aβ pathogenesis has been mechanistically defined in rodent models, much less is known regarding the relationship of APOE4 to tau pathogenesis. Recent studies have indicated a possible correlation between APOE isoform-dependent alterations in tau pathology and neurodegeneration. To explore whether neuronal expression of APOE4 triggers tauopathy, here we delivered adeno-associated viruses (AAV) expressing human APOE4 in two different models of tauopathy-rTg4510 and PS19 lines. Intracerebroventricular delivery of AAV-APOE4 in neonatal rTg4510 and PS19 mice resulted in increased APOE4 protein in neurons but did not result in altered phosphorylated tau burden, pretangle tau pathology, or silver-positive tangle pathology. Biochemical analysis of synaptic proteins did not reveal substantial alterations. Our results indicate that over-expression of APOE4 in neurons, using an AAV-mediated approache, is not sufficient to accelerate or otherwise alter the inherent tau pathology that occurs in mice overexpressing mutant human tau.

Full Text

Duke Authors

Cited Authors

  • Koller, EJ; Gonzalez De La Cruz, E; Weinrich, M; Williams, T; Cruz, PE; Ryu, D; Golde, TE; Sullivan, PM; Lewis, J; Borchelt, DR; Chakrabarty, P

Published Date

  • April 2020

Published In

Volume / Issue

  • 57 / 4

Start / End Page

  • 1986 - 2001

PubMed ID

  • 31903524

Pubmed Central ID

  • PMC7125036

Electronic International Standard Serial Number (EISSN)

  • 1559-1182

Digital Object Identifier (DOI)

  • 10.1007/s12035-019-01859-4


  • eng

Conference Location

  • United States