Neuritic Plaques - Gateways to Understanding Alzheimer's Disease

Extracellular deposits of amyloid-β (Aβ) in the form of plaques are one of the main pathological hallmarks of Alzheimer's disease (AD). Over the years, many different Aβ 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 Aβ plaque morphological subtype over the other is still unknown. Here, we review the current knowledge about neuritic plaques, a subset of Aβ plaques surrounded by swollen or dystrophic neurites, which represent the most detrimental and consequential Aβ 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 Aβ 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.