J. Neurochem. (2012) 120 (Suppl. 1), 125–139.
For nearly 100 years following the first description of this neurological disorder by Dr Alois Alzheimer, amyloid plaques and neurofibrillary tangles have been hypothesized to cause neuronal loss. With evidence that the extent of insoluble, deposited amyloid poorly correlated with cognitive impairment, research efforts focused on soluble forms of Aβ, also referred as Aβ oligomers. Following a decade of studies, soluble oligomeric forms of Aβ are now believed to induce the deleterious cascade(s) involved in the pathophysiology of Alzheimer’s disease. In this review, we will discuss our current understanding about endogenous oligomeric Aβ production, their relative toxicity in vivo and in vitro, and explore the potential future directions needed for the field.