title: Nonamyloidogenic processing of amyloid beta precursor protein is associated with retinal function improvement in aging male APPswe/PS1ΔE9 mice.
abstract: Vision declines during normal aging and in Alzheimer's disease (AD). Although the toxic role of amyloid beta (Aβ) has been established in AD pathogenesis, its influence on the aging retina is unclear. Using APPswe/PS1ΔE9 transgenic (TG) mice, a classical AD model, the retinal cell function and survival was assessed by electroretinogram (ERG) recordings and immunofluorescent stainings. Strikingly, photopic ERG measurements revealed that the retinal response mediated by cones was preserved in aging TG mice relative to WT controls. In contrast to the cortex, the expression of mutated APPsweand PS1ΔE9 did not allow to detect Aβ or amyloid plaques in 13-month-old male TG retinae. In addition, the CTFβ/CTFα ratio was significantly lower in retinal samples than that in cortical extracts, suggesting that the nonamyloidogenic pathway may endogenously limit Aβ formation in the retina of male mice. Collectively, our data suggest that retinal-specific processing of amyloid may confer protection against AD and selectively preserve cone-dependent vision during aging.
authors.affiliation: CUO-Recherche, Centre de recherche du CHU de Québec and Département d'ophtalmologie, Faculté de médecine, Université Laval, Québec, Québec, Canada.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Joly
authors.affiliation: CUO-Recherche, Centre de recherche du CHU de Québec and Département d'ophtalmologie, Faculté de médecine, Université Laval, Québec, Québec, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Lamoureux
authors.affiliation: CUO-Recherche, Centre de recherche du CHU de Québec and Département d'ophtalmologie, Faculté de médecine, Université Laval, Québec, Québec, Canada. Electronic address: vincent.pernet.1@ulaval.ca.
authors.forename: Vincent
authors.initials: V
authors.lastname: Pernet
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000502:physiology*; D000544:Alzheimer Disease / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival; D055253:Color Vision / Q000502:physiology*; D004195:Disease Models, Animal; D004596:Electroretinography; D005455:Fluorescent Antibody Technique; D008297:Male; D008822:Mice, Transgenic; D012160:Retina / Q000166:cytology / Q000378:metabolism* / Q000502:physiology*; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology
chemical_list: D016564:Amyloid beta-Protein Precursor
keywords: Aging; Alzheimer's disease; Color vision; Electroretinogram; Photoreceptors; Retina