Ultrastructural features of the blood-brain barrier in biopsy tissue from Alzheimer's disease patients

Abstract

Alzheimer's disease (AD) is a major cause of dementia. Characteristic neuropathological features of AD include neurofibrillary tangles, senile plaques, amyloid angiopathy and microvascular atrophy. The ultra-structure of the microvascular atrophy in AD and its pathogenetic significance have not been defined. This report presents an analysis of ultrastructural and morphometric features in the cerebral microvasculature of five brain biopsy specimens from AD patients. The cerebral microvasculature normally constitutes the blood-brain barrier (BBB), characterized by interendothelial tight junctions, few pinocytotic vesicles and high mitochondrial content in endothelial cells. In the AD brain biopsy tissue analyzed in the present article, data for endothelial cells were expressed as percentage of cytoplasmic area occupied by the respective organelles. The values for vesicular content ranged from 0.49% to 1.17% and were inversely correlated with mitochondrial content, which ranged from 7.04% to 2.88%. These results indicate decreased mitochondrial content and increased pinocytotic vesicles as compared to values obtained previously in endothelium from multiple sclerosis patients and in laboratory animals. Other findings such as accumulation of collagen in vascular basement membranes and focal necrotic changes in endothelial cells are further indications of BBB disruption. These data, together with earlier reports, suggest that dysfunction of the BBB is a characteristic feature of AD.