Abstract
Since the 1990s, a long series of preclinical, epidemiological, clinical, and anatomo-pathological studies have questioned the purely "degenerative" origin of Alzheimer's disease (AD), providing growing evidence of a possible "vascular" involvement in the pathogenesis of this type of dementia.Currently, evidence accumulated from preclinical, epidemiological, anatomo-pathological, clinical, neuroimaging, and proteomic studies supports a significant role of cerebral atherosclerosis in the pathogenesis of late-onset sporadic AD (LOAD). It is now well established that cerebral atherosclerosis, through various mechanisms, can promote the deposition of β-amyloid, as well as cause alterations in energy metabolism and neuronal damage.Conversely, β-amyloid can induce not only inflammation and oxidative stress, but also changes in cerebral hemodynamics, pathological angiogenesis, and endothelial dysfunction, thereby contributing to the development of cerebral atherosclerosis.Consistent data suggest that vascular phenomena may precede neurodegenerative ones. In any case, a dangerous vicious cycle is created, in which a clear separation between degenerative and vascular processes is sometimes extremely difficult to establish.