Background: Abnormalities in the human blood-brain barrier may contribute to the pathogenesis of Alzheimer disease (AD).
Experimental design: Morphometric parameters relevant to integrity of the blood-brain barrier (cerebral capillary endothelium) were assessed in brain biopsies from patients with AD and compared with values from age-matched nondemented controls.
Results: Alzheimer patients showed diminished mitochondrial density and area within cerebral capillary endothelium, an increased number of capillary profiles containing pericytes (a possible second line of defense when the capillary endothelium fails), and features of inter-endothelial junctions that suggest 'leakiness' of the blood-brain barrier.
Conclusions: The data indicate subtle but definite abnormalities suggesting compromise of the blood-brain barrier in AD that may contribute to its pathogenesis, and support neuropharmacologic and morphologic studies that suggest that a form of denervation microangiopathy may occur in AD brain, possibly secondary to loss of neurons from the pontine locus ceruleus. The changes may also play a role in the deposition of A4 Alzheimer amyloid within cerebral microvessel walls.