title: 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).
authors: Institut Universitari Barraquer, Universitat Autònoma de Barcelona, Barcelona, Spain; University Eye Clinic, Paracelsus Medical University, Salzburg, Austria. Electronic address: ralphm@barraquer.com.
authors: Ralph
authors: R
authors: Michael
authors: Medical Cell Bio Physics, University of Twente, Enschede, The Netherlands.
authors: Cees
authors: C
authors: Otto
authors: Medical Cell Bio Physics, University of Twente, Enschede, The Netherlands.
authors: Aufried
authors: A
authors: Lenferink
authors: Neurological Tissue Bank of the Biobanc-Hospital Clinic-Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors: Ellen
authors: E
authors: Gelpi
authors: Institut Universitari Barraquer, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors: Gustavo A
authors: GA
authors: Montenegro
authors: Institut Universitari Barraquer, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors: Jurja
authors: J
authors: Rosandić
authors: Department of Pathology, Institut Universitari Dexeus, Barcelona, Spain.
authors: Francisco
authors: F
authors: Tresserra
authors: Institut Universitari Barraquer, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors: Rafael I
authors: RI
authors: Barraquer
authors: Department of Ophthalmology, Leiden University Medical Center, The Netherlands.
authors: Gijs F J M
authors: GF
authors: Vrensen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D002386:Cataract / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000737:chemistry / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007908:Lens, Crystalline / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000737:chemistry*; D013059:Spectrum Analysis, Raman / Q000379:methods*
chemical_list: D016229:Amyloid beta-Peptides
keywords: Alzheimer; Raman spectroscopy; amyloid-beta; brain; cataract; hippocampus; lens