Abnormal amyloid beta metabolism in systemic abnormalities and Alzheimer's pathology: Insights and therapeutic...

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-β (Aβ peptide) in the central nervous system (CNS), whereas less is known about Aβ peptide in the periphery in AD. In this review, we provide a comprehensive summary of the current understanding of Aβ peptide metabolism (anabolism and catabolism) in the brain and periphery. We show that the abnormal metabolism of Aβ peptide is significantly linked with central-brain and peripheral abnormalities; the interaction between peripheral Aβ peptide metabolism and peripheral abnormalities affects central-brain Aβ peptide metabolism, suggesting the existence of significant communication between these two pathways of Aβ peptide metabolism. This close interaction between the central brain and periphery in abnormal Aβ 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 Aβ 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.