title: The effect of acetyl-L-carnitine and R-alpha-lipoic acid treatment in ApoE4 mouse as a model of human Alzheimer's disease.
abstract: We measured age-dependent effects of human ApoE4 on cerebral blood flow (CBF) using ApoE4 transgenic mice compared to age-matched wild-type (WT) mice by use of [(14)C] iodoantipyrene autoradiography. ApoE4 associated factors reduce CBF gradually to create brain hypoperfusion when compared to WT, and the differences in CBF are greatest as animals age from 6-weeks to 12-months. Transmission electron microscopy with colloidal gold immunocytochemistry showed structural damage in young and aged microvessel endothelium of ApoE4 animals extended to the cytoplasm of perivascular cells, perivascular nerve terminals and hippocampal neurons and glial cells. These abnormalities coexist with mitochondrial structural alteration and mitochondrial DNA overproliferation and/or deletion in all brain cellular compartments. Spatial memory and temporal memory tests showed a trend in improving cognitive function in ApoE4 mice fed selective mitochondrial antioxidants acetyl-l-carnitine and R-alpha-lipoic acid. Our findings indicate that ApoE4 genotype-induced mitochondrial changes and associated structural damage may explain age-dependent pathology seen in AD, indicating potential for novel treatment strategies in the near future.
authors.affiliation: Department of Biology and Electron Microscopy Research Center, University of Texas at San Antonio, San Antonio, TX 78249, USA.
authors.forename: Justin C
authors.initials: JC
authors.lastname: Shenk
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
authors.forename: Kathryn
authors.initials: K
authors.lastname: Fischbach
authors.forename: Kui
authors.initials: K
authors.lastname: Xu
authors.forename: Michel
authors.initials: M
authors.lastname: Puchowicz
authors.forename: Mark E
authors.initials: ME
authors.lastname: Obrenovich
authors.forename: Eldar
authors.initials: E
authors.lastname: Gasimov
authors.forename: Ludis Morales
authors.initials: LM
authors.lastname: Alvarez
authors.forename: Bruce N
authors.initials: BN
authors.lastname: Ames
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Lamanna
authors.forename: Gjumrakch
authors.initials: G
authors.lastname: Aliev