Survey of AMD and Normal Maculas for Amyloid-Beta Containing Vesicles

Abstract

Abstract: : Purpose: Amyoid-beta containing vesicles have been detected in drusen (Johnson et al., PNAS 99:11830, 2002). This finding suggests a possible link between the pathogenesis of Alzheimer's disease and AMD. The purpose of this study was to determine the frequency and distribution of amyloid-beta containing vesicles in AMD and normal age-matched eyes to gain more information about their potential role in the pathogenesis of AMD. Methods: Amyloid beta containing vesicles in 10 post mortem AMD (non-exudative or exudative) and 10 normal maculas were detected using immunohistochemistry with anti amyloid beta polyclonal 2332, and monoclonal 6E10 and 4G8. Vesicles were quantified in sections taken at regular intervals. Antibody specificity was tested by immunohistochemistry using normal and Alzheimer's brains and using amyloid beta peptide preadsorption. Results: Compared with normal maculas, AMD maculas had many more amyloid beta-containing vesicles. The vesicles were located in drusen and were detected by all three antibodies. Only a subset of drusen contained amyloid-beta labeling vesicles. Some drusen contained may vesicles, and others as few as one vesicle. Peptide blocking experiments provided evidence for antibody specificity and the antibodies detected amyloid in Alzheimer's brains. Conclusions: These results confirm the presence of amyloid beta-containing vesicles in drusen and demonstrate that only a subset of drusen contain vesicles. It is possible that either some drusen never contain vesicles, or that they are only present during certain phases of drusen development. The preponderance of amyloid-beta containing vesicles in AMD compared to normal eyes supports the hypothesis that amyloid-beta may play a role in the pathogenesis of AMD. If so, then the anti-amyloid-beta therapies under development for Alzheimer's may prove useful for AMD.

Keywords: age-related macular degeneration • immunohistochemistry • pathology: human