CEREBRAL VESSELS IN AGING AND ALZHEIMERS-DISEASE

The integrity of the cerebral vasculature is crucial to the maintenanc e of cognitive functions during ageing. Prevailing evidence suggests t hat cerebrovascular functions decline during normal ageing, with prono unced effects in Alzheimer's disease (AD). The causes of these changes largely remain unknown. While previous studies recorded ageing-relate d impairments, such as atherosclerosis and loss of innervation in basa l surface arteries of the brain, it only recently has been realized th at a number of subtle alterations in both the intracranial resistance Vessels and the smaller capillaries is apparent in both ageing animals and humans. The dominant changes include alterations in composition o f connective tissues and smooth muscle of large vessel walls, thickeni ng of the vascular basement membrane, thinning of the endothelium in s ome species, loss of endothelial mitochondria and increased pericytes. Some of these attributes appear more affected in AD. Other abnormalit ies entail profound irregularities in the course of microvessels, unex plained inclusions in the basement membrane and changes in unique prot eins and membrane lipids associated with the blood-brain barrier. Brai n imaging and permeability studies show no clear functional evidence t o support the structural and biochemical anomalies, but it is plausibl e that focal and transient breach of the blood-brain barrier in ageing , and more notably in AD, occurs. Thus, circumscribed neuronal populat ions in certain brain regions could become vulnerable. Furthermore, th e characteristic deposition of amyloid in vessels in AD may exacerbate the decline in vascular function and promote chronic hypoperfusion. A lthough not explicit from current studies, it is likely that the brain Vasculature is continually modified by growth and repair mechanisms i n attempts to maintain perfusion during ageing and disease. Copyright (C) 1996 Elsevier Science Inc.