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Cationic dyes reveal proteoglycans structurally integrated within the characteristic lesions of Alzheimer's disease

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Summary

The cationic dyes ruthenium red (RR) and cuprolinic blue (CB) were used to preserve proteoglycans (PGs) for visualization at the ultrastructural level in brain tissue from seven cases of Alzheimer's disease (obtained at autopsy within 3–4 h after death). PGs were visualized as RR-positive granules specifically localized to the amyloid fibrils in neuritic plaques. In neurofibrillary tangles, RR granules were localized to the paired helical filaments and straight filaments usually at a consistent periodicity of 40–70 nm. CB, known to preserve PGs as short punctate filaments, also demonstrated PGs specifically localized to the amyloid fibrils in neuritic plaques and in association with paired helical filaments and straight filaments in neurofibrillary tangles. Persistent staining with CB at magnesium chloride concentrations of 0.3 and 0.7 M in the neuritic plaques suggested the presence of highly sulfated PGs, whereas abolishment of CB staining at 0.7 M magnesium chloride in the neurofibrillary tangles implied that different PGs and/or glycosaminoglycans were present in the neurofibrillary tangles. The specific ultrastructural localization of PGs to the characteristic lesions in Alzheimer's disease suggests that PGs are part of a complex structural network with amyloid fibrils in neuritic plaques and the filamentous structures present in neurofibrillary tangles.

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Supported by the Alzheimer's Disease Research Program of the American Health Assistance Foundation, The Alzheimer's Disease and Related Disorders Association Pilot Grant 87-019 and the Friends of Alzheimer's Research in conjunction with the University of Washington Alzheimer's Disease Research Center

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Snow, A.D., Lara, S., Nochlin, D. et al. Cationic dyes reveal proteoglycans structurally integrated within the characteristic lesions of Alzheimer's disease. Acta Neuropathol 78, 113–123 (1989). https://doi.org/10.1007/BF00688198

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