The neuropathology of Alzheimer's disease

This article characterizes the major pathologic changes in Alzheimer's disease (AD) brain with A beta deposition and neurofibrillary degeneration of neurons, leading to severe neuronal loss and brain atrophy. Currently, neuropathologists recognize plaques associated with fibrillar amyloid-beta and extensive damage of the neuropil (neuritic, thioflavine-S-positive or malignant plaques) and plaques that do not contain fibrils (diffuse, thioflavine-negative or benign plaques). The cellular origin of these two subclasses appears to be different: neurons seem to produce diffuse, nonfibrillar, benign plaques, whereas microglia and perivascular cells appear to produce fibrillar deposits in brain parenchyma. Smooth muscle cells are the source of sA beta, which polymerizes in the basement membrane of leptomeningeal and cortical arteries and veins. This new classification of A beta deposits, according to the origin of amyloid, elucidates the morphologic variability of changes and opens new avenues for development of therapeutic strategies for AD.