Absence of amyloid-beta in lenses of Alzheimer patients: A confocal Raman microspectroscopic study

Abstract

We have compared the protein profiles in plaques and tangles in the hippocampus of post-mortem Alzheimer brains and in opaque and clear regions in the deep cortex of eye lenses of the same donors. From the 7 Alzheimer donors studied, 1 had pronounced bilateral cortical lens opacities, 1 moderate and 5 only minor or no cortical opacities. We focused on beta-sheet levels, a hallmarking property of amyloid-beta, the major protein of plaques and tau protein, the major protein of tangles in Alzheimer brains. Confocal Raman microspectroscopy and imaging was used in combination with hierarchical cluster analysis. Plaques and tangles show high levels of beta-sheets with a beta-sheet to protein ratio of 1.67. This ratio is 1.12 in unaffected brain tissue surrounding the plaques and tangles. In the lenses this ratio is 1.17 independently of the presence or absence of opacities. This major difference in beta-sheet conformation between hippocampus and lens is supported by Congo red and immunostaining of amyloid-beta and tau which were positive for plaques and tangles in the hippocampus but fully negative for the lens irrespective of the presence or absence of opacities. In line with a previous study (Michael et al., 2013) we conclude that cortical lens opacities are not typical for Alzheimer patients and are not hallmarked by accumulation of amyloid-beta, and can thus not be considered as predictors or indicators of Alzheimer disease as claimed by Goldstein et al. (2003).