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

Autor: Koller EJ; Department of Neuroscience, University of Florida, Gainesville, FL, 32610, USA.; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA., Gonzalez De La Cruz E; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA., Weinrich M; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA., Williams T; Department of Neuroscience, University of Florida, Gainesville, FL, 32610, USA.; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA., Cruz PE; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA., Ryu D; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA., Golde TE; Department of Neuroscience, University of Florida, Gainesville, FL, 32610, USA.; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA.; McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA., Sullivan PM; Department of Medicine, Duke University, Durham VA Geriatric Research, Education and Clinical Center, Durham, NC, 27710, USA., Lewis J; Department of Neuroscience, University of Florida, Gainesville, FL, 32610, USA.; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA.; McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA., Borchelt DR; Department of Neuroscience, University of Florida, Gainesville, FL, 32610, USA.; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA.; McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA., Chakrabarty P; Department of Neuroscience, University of Florida, Gainesville, FL, 32610, USA. pchakrabarty@ufl.edu.; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA. pchakrabarty@ufl.edu.; McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA. pchakrabarty@ufl.edu.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2020 Apr; Vol. 57 (4), pp. 1986-2001. Date of Electronic Publication: 2020 Jan 06.
DOI: 10.1007/s12035-019-01859-4
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz: