Amyloid-Peptide Vaccinations Reduce β-Amyloid Plaques but Exacerbate Vascular Deposition and Inflammation in the Retina of Alzheimer's Transgenic Mice

Alzheimer's disease (AD) is pathologically characterized by accumulation of beta-amyloid (A beta) protein deposits and/or neurofibriffary 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 A beta plaques in the retinas of APPswe/PS1 Delta E9 transgenic mice. We now report the detection of A beta plaques with increased retinal microvascular deposition of A beta and neuroinflammation in Tg2576 mouse retinas. The majority of A beta-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 A beta plaques in adjacent sections. Although A beta vaccinations reduced retinal A beta deposits, there was a marked increase in retinal microvascular A beta 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. (Am J Pathol 2009, 175:2099-2110; DOI: 10.2353/ajpath.2009.090159)