beta-Amyloid converts an acute phase injury response to chronic injury responses.

As the brain ages, amyloid deposits accumulate and, as these deposits condense into a beta-sheet conformation, they contribute to the organization of cellular responses and maintain a chronic level of stimulation and injury. Furthermore, accompanying reactions can lead to the production of additional beta-amyloid, the build up of additional fibrillar beta-amyloid, and prolongation of the response. As it accumulates, beta-amyloid appears to develop properties that drive many signal transduction processes in the classic injury cascade and also activate complement, which results in an amplified beta-amyloid AD cascade. In this way several mechanisms, although apparently independent, proceed in parallel, reinforce each other, and perpetuate pathology and structural damage to the brain. Specifically, we suggest that via the activation of complement, initiation, and perpetuation of other cascades, and its own direct toxic actions, beta-amyloid converts an acute response to injury into a chronic damaging inflammatory reaction thereby contributing to neuronal dysfunction and degeneration.