Multiple disregulations lipid metabolism have been reported in brain of Alzheimer’s disease (AD) patients and in transgenic mice models of the disease. As the consequence, the lipid composition and structural organization of lipid rafts from the frontal and temporal cortices of AD patients was deeply altered. Altered lipid raft organization seems to affect APP biology triggering those molecular events that ultimately lead to the onset of AD in several different ways: 1) by modulating the functions of APP as signaling molecule; 2) by shifting the proteolytic processing of APP in an amyloidogenic direction. Lipid rafts contain not only APP, but also APP-derived proteolytic fragments, including A?? and several proteolytic enzymes involved in APP processing, in particular they are enriched in active and -secretases, and seem to be the main cellular site where the amyloidogenic processing of APP occurs, leading to the production of A amyloid; 3) by favoring the conversion of soluble A to the insoluble form; 4) by affecting amyloid-indepentent mechanisms of neuronal death.
Thus, alterations in the membrane structure and organization play multifaceted and pivotal roles in the pathogenesis of the disease.
Multiple disregulations lipid metabolism have been reported in brain of Alzheimer’s disease (AD) patients and in transgenic mice models of the disease. As the consequence, the lipid composition and structural organization of lipid rafts from the frontal and temporal cortices of AD patients was deeply altered. Altered lipid raft organization seems to affect APP biology triggering those molecular events that ultimately lead to the onset of AD in several different ways: 1) by modulating the functions of APP as signaling molecule; 2) by shifting the proteolytic processing of APP in an amyloidogenic direction. Lipid rafts contain not only APP, but also APP-derived proteolytic fragments, including A?? and several proteolytic enzymes involved in APP processing, in particular they are enriched in active and -secretases, and seem to be the main cellular site where the amyloidogenic processing of APP occurs, leading to the production of A amyloid; 3) by favoring the conversion of soluble A to the insoluble form; 4) by affecting amyloid-indepentent mechanisms of neuronal death.
Thus, alterations in the membrane structure and organization play multifaceted and pivotal roles in the pathogenesis of the disease.
