Published online before print October 15, 2009

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(American Journal of Pathology. 2009;175:2099-2110.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.090159

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

Bingqian Liu^*, Suhail Rasool, Zhikuan Yang, Charles G. Glabe, Steven S. Schreiber^*¶||, Jian Ge and Zhiqun Tan^*

From the Departments of Neurology,^* Molecular Biology and Biochemistry, and Anatomy and Neurobiology,|| and the Institute for Memory Impairments and Neurological Disorders, University of California Irvine School of Medicine, Irvine, California; the State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China; and the VA Long Beach Healthcare System,^¶ Long Beach, California

Alzheimer’s disease (AD) is pathologically characterized by accumulation of β-amyloid (Aβ) 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 Aβ plaques in the retinas of APPswe/PS1E9 transgenic mice. We now report the detection of Aβ plaques with increased retinal microvascular deposition of Aβ and neuroinflammation in Tg2576 mouse retinas. The majority of Aβ-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 Aβ plaques in adjacent sections. Although Aβ vaccinations reduced retinal Aβ deposits, there was a marked increase in retinal microvascular Aβ 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.