The Role of Synaptic Dysfunction in Alzheimer's Disease

Abstract

Deemed as incurable, Alzheimer's disease (AD) research is becoming less convoluted as our understanding of its pathology increases. With current treatments focusing on merely mitigating the symptoms of AD, there have been many attempts to find a molecular culprit to serve as the single underlying cause and therapeutic target for clinical applications to approach the disease from its roots. Indeed, over the course of decades, the endless search for a singular target culprit in AD has uncovered a cascade of pathological defects, adding on to each other throughout the progression of the disease. The developmental patterns of amyloid-β (Aβ) oligomers have been studied as a means to discover the complex molecular interplay between various immune responses, genetic mutations, pathway disturbances, and regulating factors that disturb synapse homeostasis before disease manifestation. This new understanding has shifted the underlying goal of the research community from merely removing Aβ oligomers to finding methods that can predict high risk individuals and resorting to cocktail-drug treatments in an attempt to regulate multiple pathways that cumulatively result in the debilitating symptoms of the disease. By utilizing various assays from immuno-targeting to molecular biomarkers, we then interfere in the molecular cascades in an endeavor to avoid synapse dysfunction before disease maturity. Here, we review the current literature supporting the importance of synapses in AD, our current understanding of the molecular interactions leading up to clinical diagnoses, and the techniques used in targeted therapies.

Keywords: Alzheimer’s disease; amyloid-β oligomers; biomarker; long-term depression; long-term potentiation; synapse.