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lüll Membrane rafts in Alzheimer s disease beta-amyloid production Vetrivel KS; Thinakaran GBiochim Biophys Acta 2010[Aug]; 1801 (8): 860-7Alzheimer's disease (AD), the most common age-associated dementing disorder, is pathologically manifested by progressive cognitive dysfunction concomitant with the accumulation of senile plaques consisting of amyloid-beta (Abeta) peptide aggregates in the brain of affected individuals. Abeta is derived from a type I transmembrane protein, amyloid precursor protein (APP), by the sequential proteolytic events mediated by beta-site APP cleaving enzyme 1 (BACE1) and gamma-secretase. Multiple lines of evidence have implicated cholesterol and cholesterol-rich membrane microdomains, termed lipid rafts in the amyloidogenic processing of APP. In this review, we summarize the cell biology of APP, beta- and gamma-secretases and the data on their association with lipid rafts. Then, we will discuss potential raft targeting signals identified in the secretases and their importance on amyloidogenic processing of APP.|Alzheimer Disease/*metabolism[MESH]|Amyloid Precursor Protein Secretases/metabolism[MESH]|Amyloid beta-Peptides/*metabolism[MESH]|Animals[MESH]|Cell Biology[MESH]|Humans[MESH]|Membrane Microdomains/metabolism/*physiology[MESH]|Models, Biological[MESH]|Protein Processing, Post-Translational/physiology[MESH] |