Beta-amyloid pathology in human brain microvessel extracts from the parietal cortex: relation with cerebral amyloid angiopathy and Alzheimer ’s disease

In this study, we validated by Western, ELISA and immunofluorescence analyses a procedure to generate microvasculature-enriched fractions from frozen samples of human cerebral cortex. We then investigated Aβ and proteins involved in its clearance or production in microvessel extract s generated from the parietal cortex of 60 volunteers in the Religious Orders Study. Volunteers were categorized as AD (n = 38) or controls (n = 22) based on the ABC scoring method presented in the revised guidelines for the neuropathological diagnosis of AD. Higher ELISA-determined concentrations of vascular Aβ40 and Aβ42 were found in persons with a neuropathological diagnosis of AD, in apoE4 carriers and in participants with adv anced parenchymal CAA, compared to respective age-matched controls. Vascular levels of two proteins involved in Aβ clearance, ABCB1 and neprilysin, were lower in persons with AD and positively correlated with cognitive function, while being inversely correlated to vascular Aβ40. In contrast, BACE1 , a protein necessary for Aβ production, was increased in individuals with AD and in apoE4 carriers, negatively correlated to cognitive function and positively correlated to Aβ40 in microvessel extracts. The present report indicates that concentrating microvessels from frozen human brain samples f acilitates the quantitative biochemical analysis of cerebrovascular dysfunction in CNS disorders. Data generated overall show that microvessels extracted from individ...
Source: Acta Neuropathologica - Category: Neurology Source Type: research