Neuritic Plaques - Gateways to Understanding Alzheimer's Disease

Extracellular deposits of amyloid-beta (A beta) in the form of plaques are one of the main pathological hallmarks of Alzheimer's disease (AD). Over the years, many different A beta plaque morphologies such as neuritic plaques, dense cored plaques, cotton wool plaques, coarse-grain plaques, and diffuse plaques have been described in AD postmortem brain tissues, but correlation of a given plaque type with AD progression or AD symptoms is not clear. Furthermore, the exact trigger causing the development of one A beta plaque morphological subtype over the other is still unknown. Here, we review the current knowledge about neuritic plaques, a subset of A beta plaques surrounded by swollen or dystrophic neurites, which represent the most detrimental and consequential A beta plaque morphology. Neuritic plaques have been associated with local immune activation, neuronal network dysfunction, and cognitive decline. Given that neuritic plaques are at the interface of A beta deposition, tau aggregation, and local immune activation, we argue that understanding the exact mechanism of neuritic plaque formation is crucial to develop targeted therapies for AD.