Is Alzheimer’s disease amyloidosis the result of a repair mechanism gone astray?

摘要

We synthesize several lines of evidence supporting the hypothesis that at least one function of Aβ 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 acute 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 an Aβ 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 may not represent the preeminent factor in dementia pathogenesis. Successful application of AD preventative approaches may hinge on an accurate and comprehensive view of co-morbidities, including cardiovascular disease, diabetes and head trauma.