Absence of amyloid beta in human lens opacities: A confocal Raman study

Purpose Amyloid beta, the main protein component of Alzheimer (AD) plaques and tangles, is characterized by high levels of beta‐sheets. Raman microspectroscopy allows quantitative analysis of this specific molecular conformation. We compared the beta‐sheet levels in lens opacities and in plaques and tangles in the hippocampus of AD patients. Methods We obtained 14 lenses from 7 post‐mortem donors , neuropathologically confirmed as having advanced or moderate AD. From 3 of these donors, we also obtained hippocampus tissue. Protein and lipid conformations were analysed in the 500‐1800 cm‐1 fingerprint region. The ratio of the beta‐sheet peak at 1668 cm‐1 and the protein peak at 1450 cm‐1 is a quantitative measure for the beta‐sheet content. Additionally, histological sections were stained using a standard Congo red protocol and amyloid beta immunohistochemistry. Results The 1668cm‐1/1450cm‐1 ratio, quantitatively reflecting the beta‐sheet content, is 1.28 for clear and cataractous regions in the lens.For the plaques and tangles in the hippocampus the ratio is 1.62 and 1.23 for non‐affected regions. When corrected for the presence of lipids in plaques and tangles this ratio is 2.64. Congo red and amyloid beta immunohistochemistry is positive for AD plaques and tangles but is negative for all lenses studied. Conclusion In contrast with a previous study (Goldstein et al. 2003) we conclude that proteins in opaque regions of lenses and in hippocampal plaques and tangles are fully different species. Moreover opacification is not accompanied by changes in the beta‐sheet configuration of lens proteins. This means that cortical cataract cannot be considered as an indicator and predictor of AD.