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Rogaeva E Meng Y Lee JH Gu Y Kawarai T Zou F Katayama T Baldwin CT Cheng R Hasegawa H Chen F Shibata N Lunetta KL Pardossi-Piquard R Bohm C Wakutani Y Cupples LA Cuenco KT Green RC Pinessi L Rainero I Sorbi S Bruni A Duara R Friedland RP Inzelberg R Hampe W Bujo H Song YQ Andersen OM Willnow TE Graff-Radford N Petersen RC Dickson D Der SD Fraser PE Schmitt-Ulms G Younkin S Mayeux R Farrer LA St George-Hyslop P 《Nature genetics》2007,39(2):168-177
The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease. 相似文献
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The basaltic rock in the lower part of the thick Holyoke lava flow in Connecticut and Massachusetts has been shown to have a remarkable texture, with crystals of feldspar linked together in a continuous three-dimensional network of chains. Heating experiments have revealed that this network persists to temperatures where the rock is 75% liquid, and therefore the network was interpreted to have formed at an early stage of crystallization and to have played an important role in the compaction of crystal mush in the lower part of the flow. Despite the texture's importance to our understanding of how such basalt flows form, the origin of the texture has remained uncertain. Here we show that, although the network is present in the lower third of the flow, it was actually formed in the upper solidification front and was transported down in plumes of dense crystal mush. Convection of this type has been postulated for intrusive magma chambers, but corroborative field evidence has been equivocal, especially in lava lakes and flows. Preservation of the roof-generated texture in the lower part of a thick flood-basalt flow therefore constitutes important evidence for the role of convection in the solidification and differentiation of a simple magma sheet. 相似文献
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