Amyloid Beta Dynamics in Biological Fluids-Therapeutic Impact.

Despite the significant impact of Alzheimer's disease (AD) at individual and socioeconomic levels and the numerous research studies carried out on this topic over the last decades, the treatments available in daily clinical practice remain less than satisfactory. Among the accepted etiopathogenic hypotheses, the amyloidogenic pathway theory, although intensively studied and even sometimes controversial, is still providing relevant theoretical elements for understanding the etiology of AD and for the further development of possible therapeutic tools. In this sense, this review aims to offer new insights related to beta amyloid (Aβ), an essential biomarker in AD. First the structure and function of Aβ in normal and pathological conditions are presented in detail, followed by a discussion on the dynamics of Aβ at the level of different biological compartments. There is focus on Aβ elimination modalities at central nervous system (CNS) level, and clearance via the blood-brain barrier seems to play a crucial/dominant role. Finally, different theoretical and already-applied therapeutic approaches for CNS Aβ elimination are presented, including the recent "peripheral sink therapeutic strategy" and "cerebrospinal fluid sinks therapeutic strategy". These data outline the need for a multidisciplinary approach designed to deliver a solution to stimulate Aβ clearance in more direct ways, including from the cerebrospinal fluid level.