Chapter 6: Aggregation Species of Amyloid-β and Tau Oligomers in Alzheimer's Disease: Role in Therapeutics and Diagnostics Check Access

The accumulation of two types of aggregates – extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) of microtubule-associated protein Tau – constitutes the pathophysiology of Alzheimer's disease. The process of aggregation generates various intermediate species before attaining fibrillar form. The oligomeric species are considered to be highly toxic as they are the active forms during aggregation, which have the capability to spread to other cells and can ‘seed’ further aggregation. Various pathways for oligomer propagation viz. the exosomal pathway, bulk endocytosis and receptor-mediated internalization have been proposed, which lead to synaptic loss and cognitive decline. The isolation, preparation, detection and characterization of oligomeric forms are of utmost importance for designing therapeutics against them or for diagnostic purposes. However, it is difficult due to their transient nature and heterogeneity. Here, we have provided an account of the aggregation pathways of Aβ and Tau, focussing on the properties of oligomers, their propagation as well as methods and techniques for their detection, preparation and characterization. We discuss the pathophysiological aspects of the soluble oligomeric population in neuronal and glial cells and provide a brief account on the therapeutics and diagnostic role of oligomers with respect to current strategies and future perspectives.