Revisiting the role of brain and peripheral Aβ in the pathogenesis of Alzheimer's disease

Amyloid beta (A beta) is an intricate molecule that interacts with several biomolecules and/or produces insoluble assemblies and eventually the nonphysiological depositions of its alternate with normal neuronal conditions leading to Alzheimer's disease (AD). A beta is formed through the proteolytic cleavage of the amyloid precursor protein (APP). Significant efforts are being made to explore the exact role of A beta in AD pathogenesis. It is believed that the deposition of A beta in the brain takes place from A beta components which are derived from the brain itself. However, recent evidence suggests that A beta derived also from the periphery and hence the A beta circulating in the blood is capable of penetrating the blood-brain barrier (BBB) and the role of A beta derived from the periphery is largely unknown so far. Therefore, A beta origin determination and the underlying mechanisms of its pathological effects are of considerable interest in exploring effective therapeutic strategies. The purpose of this review is to provide a novel insight into AD pathogenesis based on A beta in both the brain and periphery and highlight new therapeutic avenues to combat AD pathogenesis.