Cerebrovascular degeneration is related to amyloid-beta protein deposition in Alzheimer's disease.
Current evidence is not inconsistent with the suggestion that cerebrovascular functions decline during normal aging with pronounced effects in both sporadic and familial Alzheimer's disease (AD). The primary causes of these changes remain unknown. It is possible that amyloid beta (A beta) protein is involved in the degeneration of both the larger penetrating vessels as well as the cerebral capillaries that represent the blood-brain barrier (BBB). A beta-induced endothelial changes could also alter muscular tone, resulting not only in increased expression of vascular amyloid precursor protein (APP) and production of A beta, but also in oxidative injury. We used immunochemical methods to examine the status of the perfusing cerebral vessels and the microvascular endothelium in relation to deposition of A beta in AD and non-AD aging control subjects. Double-immunostaining with antibodies to vascular markers revealed marked loss of smooth muscle in larger vessels and absence or attenuation of the endothelium in capillary profiles that still appeared to retain their basement membranes. These vascular changes were predominantly restricted to neocortical regions abundant in A beta deposits. Quantitative studies showed that the microvascular abnormalities were correlated to A beta deposition rather than neurofibrillary tangles or neuronal numbers. Our studies suggest that A beta, irrespective of its origin within vascular myocytes or brain parenchyma, is responsible not only for cerebral amyloid angiopathy, but also for the degeneration of the cerebral microvasculature, which may profoundly affect brain perfusion and BBB functions.
Kalaria
R N
RN
Department of Neurology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000098:blood supply; D002543:Cerebral Hemorrhage / Q000473:pathology; D002560:Cerebrovascular Circulation; D004730:Endothelium, Vascular / Q000473:pathology; D006801:Humans; D008833:Microcirculation; D009131:Muscle, Smooth, Vascular / Q000473:pathology
D016229:Amyloid beta-Peptides