Neurovascular mechanisms of Alzheimer's neurodegeneration.
In contrast to traditional neuroncentric views of Alzheimer's disease (AD), recent findings indicate that neurovascular dysfunction contributes to cognitive decline and neurodegeneration in AD. Here, I propose the neurovascular hypothesis of AD, suggesting that faulty clearance of amyloid beta peptide (A beta) across the blood-brain barrier (BBB), aberrant angiogenesis and senescence of the cerebrovascular system could initiate neurovascular uncoupling, vessel regression, brain hypoperfusion and neurovascular inflammation. Ultimately, this would lead to BBB compromise, to chemical imbalance in the neuronal environment and to synaptic and neuronal dysfunction, injury and loss. Based on the neurovascular hypothesis, I suggest an array of new potential therapeutic approaches that could be developed for AD, to enhance A beta clearance and neurovascular repair, and to protect the neurovascular unit from divergent inducers of injury and apoptosis.
Zlokovic
Berislav V
BV
Frank P. Smith Laboratories for Neuroscience and Neurological Surgery Research, Department of Neurological Surgery and Division of Neurovascular Biology, University of Rochester Medical Center, Rochester, NY 14642, USA. berislav_zlokovic@urmc.rochester.edu
D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000503:physiopathology; D001921:Brain / Q000098:blood supply* / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D006801:Humans; D008959:Models, Neurological; D009410:Nerve Degeneration / Q000209:etiology* / Q000473:pathology
D016229:Amyloid beta-Peptides