Alzheimer-Associated Pathology in the Extracellular Space

A clear indicator for the end of the unusually protracted initial phase of the AD-associated pathological process is the abrupt appearance of an additional protein that appears in soluble form in the ISF: the small, i.e., 38–43, but mostly 40 or 42, amino acid-containing hydrophobic amyloid-β (Aβ) protein, that at first is diffusely distributed in a monomeric state in a few circumscribed regions of the ISF but then rapidly forms insoluble aggregations, most of which are plaque-like entities. These Aβ-plaques develop with such consistency in the course of AD that they constitute one of its hallmark lesions (Masters and Selkoe 2012).