The role of oxidative stress in the pathophysiology of cerebrovascular lesions in Alzheimer's disease.
Alzheimer's disease (AD) and stroke are two leading causes of age-associated dementia. A rapidly growing body of evidence indicates that increased oxidative stress from reactive oxygen radicals is associated with the aging process and age-related degenerative disorders such as atherosclerosis, ischemia/reperfusion, arthritis, stroke, and neurodegenerative diseases. New evidence has also indicated that vascular lesions are a key factor in the development of AD. This idea is based on a positive correlation between AD and cardiovascular and cerebrovascular diseases such as arterio- and atherosclerosis and ischemia/reperfusion injury. In this review we consider recent evidence supporting the existence of an intimate relationship between oxidative stress and vascular lesions in the pathobiology of AD. We also consider the opportunities for therapeutic interventions based on the molecular pathways involved with these causal relationships.
Aliev
Gjumrakch
G
Electron Microscopy Center, and Department of Anatomy, Case Western Reserve University, School of Medicine and University Hospital of the Cleveland, OH 44106-4938, USA. gxa15@po.cwru.edu
Smith
Mark A
MA
Seyidov
Dilara
D
Neal
Maxwell Lewis
ML
Lamb
Bruce T
BT
Nunomura
Akihiko
A
Gasimov
Eldar K
EK
Vinters
Harry V
HV
Perry
George
G
LaManna
Joseph C
JC
Friedland
Robert P
RP
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D002536:Cerebral Arteries / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D002560:Cerebrovascular Circulation / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*