Abnormal amyloid beta metabolism in systemic abnormalities and Alzheimer's pathology: Insights and therapeutic approaches from periphery

Abstract

Alzheimer's disease (AD) is an age-associated, multifactorial neurodegenerative disorder that is incurable. Despite recent success in treatments that partially improve symptomatic relief, they have failed in most clinical trials. Re-holding AD for accurate diagnosis and treatment is widely known as a challenging task. Lack of knowledge of basic molecular pathogenesis might be a possible reason for ineffective AD treatment. Historically, a majority of therapy-based studies have investigated the role of amyloid-beta (A beta peptide) in the central nervous system (CNS), whereas less is known about A beta peptide in the periphery in AD. In this review, we provide a comprehensive summary of the current understanding of A beta peptide metabolism (anabolism and catabolism) in the brain and periphery. We show that the abnormal metabolism of A beta peptide is significantly linked with central-brain and peripheral abnormalities; the interaction between peripheral A beta peptide metabolism and peripheral abnormalities affects central-brain A beta peptide metabolism, suggesting the existence of significant communication between these two pathways of A beta peptide metabolism. This close interaction between the central brain and periphery in abnormal A beta peptide metabolism plays a key role in the development and progression of AD. In conclusion, we need to obtain a full understanding of the dynamic roles of A beta peptide at the molecular level in both the brain and periphery in relation to the pathology of AD. This will not only provide new information regarding the complex disease pathology, but also offer potential new clues to improve therapeutic strategies and diagnostic biomarkers for the successful treatment of AD.