Small vessel disease and Alzheimer's dementia: pathological considerations.
Current evidence suggests that the neuropathology of Alzheimer type of dementia comprises more than amyloid plaques and neurofibrillary tangles. At least a third of Alzheimer disease (AD) cases may exhibit significant cerebrovascular pathology, which constitutes distinct small vessel disease (SVD). Cerebral amyloid angiopathy, microvascular degeneration affecting the cerebral endothelium and smooth muscle cells, basal lamina alterations, hyalinosis and fibrosis are often evident in AD. These changes may be accompanied by perivascular denervation that is causal in the cognitive decline of AD. Amyloid beta protein may cause degeneration of both the larger perforating arterial vessels as well as cerebral capillaries, which represent the blood-brain barrier. In addition, macro- and microinfarctions, haemorrhages, lacunes and ischaemic white matter changes are also present in AD. The development of SVD in late-onset AD may engage an interaction of perivascular mediators as well as circulation-derived factors that perturb the brain vasculature. Peripheral vascular disease such as long-standing hypertension, atrial fibrillation, coronary or carotid artery disease and diabetes could further modify the cerebral circulation such that a sustained hypoperfusion or oligaemia is impacted upon the ageing brain.
Kalaria
Raj N
RN
Institute for Ageing and Health, Newcastle General Hospital, and Department of Psychiatry, University of Newcastle, Newcastle upon Tyne, UK. r.n.kalaria@ncl.ac.uk
D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology*; D001057:Apolipoproteins E / Q000378:metabolism; D002462:Cell Membrane / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000473:pathology*; D016228:Endothelial Growth Factors / Q000502:physiology; D006801:Humans; D008222:Lymphokines / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000473:pathology; D011506:Proteins / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D001057:Apolipoproteins E; D016228:Endothelial Growth Factors; D008222:Lymphokines; D011506:Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors