Back to the Plaque: Emerging Studies That Refocus Attention on the Neuritic Plaque in Alzheimer’s Disease

Publisher Summary This chapter describes the cardinal features of the neuritic plaque (NP) and the changing context in which these features have been viewed relative to disease pathogenesis. Alzheimer's disease (AD) is the most common neurological disorder of advanced aging, affecting nearly one in ten individuals over the age of 65 years. AD leads to profound impairments in memory and executive function and places a tremendous burden on society with regard to patient care costs, lost productivity, and high burden on caregivers. The most definitive diagnosis of AD is a postmortem examination of the brain for the presence of two characteristic lesions: NP and the neurofibrillary tangle. The chapter revisits the key observations in the literature that deemphasizes the pathologic role of NPs in AD, in parallel with more recent findings that have begun to refocus attention toward the NP as a potential causal factor in the development of AD. It also proposes sequence of events leading to the formation of NPs and ultimately to clinical AD and explores the therapeutic implications of focusing on targets related to NPs.