title: Amyloid-peptide vaccinations reduce {beta}-amyloid plaques but exacerbate vascular deposition and inflammation in the retina of Alzheimer's transgenic mice.
abstract: Alzheimer's disease (AD) is pathologically characterized by accumulation of beta-amyloid (Abeta) protein deposits and/or neurofibrillary tangles in association with progressive cognitive deficits. Although numerous studies have demonstrated a relationship between brain pathology and AD progression, the Alzheimer's pathological hallmarks have not been found in the AD retina. A recent report showed Abeta plaques in the retinas of APPswe/PS1DeltaE9 transgenic mice. We now report the detection of Abeta plaques with increased retinal microvascular deposition of Abeta and neuroinflammation in Tg2576 mouse retinas. The majority of Abeta-immunoreactive plaques were detected from the ganglion cell layer to the inner plexiform layer, and some plaques were observed in the outer nuclear layer, photoreceptor outer segment, and optic nerve. Hyperphosphorylated tau was labeled in the corresponding areas of the Abeta plaques in adjacent sections. Although Abeta vaccinations reduced retinal Abeta deposits, there was a marked increase in retinal microvascular Abeta deposition as well as local neuroinflammation manifested by microglial infiltration and astrogliosis linked with disruption of the retinal organization. These results provide evidence to support further investigation of the use of retinal imaging to diagnose AD and to monitor disease activity.
authors.affiliation: Department of Neurology, University of California Irvine School of Medicine, USA.
authors.forename: Bingqian
authors.initials: B
authors.lastname: Liu
authors.forename: Suhail
authors.initials: S
authors.lastname: Rasool
authors.forename: Zhikuan
authors.initials: Z
authors.lastname: Yang
authors.forename: Charles G
authors.initials: CG
authors.lastname: Glabe
authors.forename: Steven S
authors.initials: SS
authors.lastname: Schreiber
authors.forename: Jian
authors.initials: J
authors.lastname: Ge
authors.forename: Zhiqun
authors.initials: Z
authors.lastname: Tan
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D016874:Neurofibrillary Tangles / Q000473:pathology*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D012171:Retinal Vessels / Q000378:metabolism / Q000473:pathology*; D014611:Vaccination
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments