title: Is Alzheimer's disease amyloidosis the result of a repair mechanism gone astray?
abstract: Here, we synthesize several lines of evidence supporting the hypothesis that at least one function of amyloid-β is to serve as a part of the acute response to brain hemodynamic disturbances intended to seal vascular leakage. Given the resilient and adhesive physicochemical properties of amyloid, an abluminal hemostatic repair system might be highly advantageous, if deployed on a limited and short-term basis, in young individuals. However, in the aged, inevitable cardiovascular dysfunction combined with brain microvascular lesions may yield global chronic hypoperfusion that may lead to continuous amyloid deposition and consequential negative effects on neuronal viability. A large body of experimental evidence supports the hypothesis of an amyloid-β rescue function gone astray. Preventing or inducing the removal of amyloid in Alzheimer's disease (AD) has been simultaneously successful and disappointing. Amyloid deposits clearly play major roles in AD, but they may not represent the preeminent factor in dementia pathogenesis. Successful application of AD preventative approaches may hinge on an accurate and comprehensive view of comorbidities, including cardiovascular disease, diabetes, and head trauma.
authors: The Longtine Center for Neurodegenerative Biochemistry, Banner Sun Health Research Institute, Sun City, AZ, USA.
authors: Tyler A
authors: TA
authors: Kokjohn
authors: Chera L
authors: CL
authors: Maarouf
authors: Alex E
authors: AE
authors: Roher
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D016657:Cerebral Amyloid Angiopathy / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D006801:Humans
chemical_list: D016229:Amyloid beta-Peptides