INCREASED COLLAGEN CONTENT OF CEREBRAL MICROVESSELS IN ALZHEIMERS-DISEASE

Based on previous evidence suggesting abnormalities in the brain micro vasculature, we examined basement membrane collagen in isolated cerebr al microvessels (CMV) from subjects with Alzheimer's disease (AD) and age-matched controls. Concentrations of hydroxyproline, the principal constituent of collagen IV, were significantly increased by 55% in CMV from AD subjects compared to controls. This result was corroborated b y the finding of 60% increased total collagen content in CMV as eviden t by the selective binding of Sirius red dye. Hydroxyproline and colla gen concentrations in samples of cerebral cortex assayed in parallel w ere 6-20 times smaller than in CMV and were not changed between contro ls and AD subjects. To further differentiate AD and control samples, f ractions of CMV were solubilized and the pepsin digested collagen prot eins resolved by SDS-PAGE. Upon immunoblotting, AD samples with increa sed collagen revealed proportionally greater specific immunoreactiviti es detected by antibodies to collagen IV. Our observations suggest alt ered collagen IV content of cerebral vessels in subjects with AD that may affect brain microvascular functions.