From brain ischemia-reperfusion injury to possible sporadic Alzheimer's disease

Understanding of the molecular basis of dementias such as Alzheimer's disease has not improved greatly in recent years. In this situation the study of neurobiology of Alzheimer's disease, now more than ever, needs an infusion of new concept. Recent evidence suggests that the neuropathological picture of Alzheimer's disease comprises more than amyloid accumulation, neurofibrillary tangles and finally brain atrophy. At least one third of Alzheimer type of dementia cases exhibit different cerebrovascular diseases. In addition, micro- and macroinfarctions and ischemic white matter changes are also evident in brains of Alzheimer's disease patients. The presence of vascular abnormalities seems usually ignored and regarded by researchers as insignificant or considered incidental in Alzheimer's disease etiology. The "ischemia-reperfusion hypothesis" was primarily aimed at stimulating research and redirecting the focus of studies towards ischemic cellular mechanisms of Alzheimer's disease. Considerable progress has been made in recent years in understanding the role of ischemia in the aging process and in contributing to the development of Alzheimer's disease. To accommodate the recent ischemic progress of study in Alzheimer's disease there is a need to synthesize all the divergent pieces of data into a coherent story. In this review, current knowledge on the relation between cerebrovascular disease factors and Alzheimer's type dementia will be reviewed. We will summarize the results with a special focus on Alzheimer lesions in experimental brain ischemia.