Microarray Analysis of Hippocampal CA1 Neurons Implicates Early Endosomal Dysfunction During Alzheimer's Disease Progression
Stephen D. Ginsberg,Stephen D. Ginsberg,Melissa J. Alldred,Melissa J. Alldred,Scott E. Counts,Anne M. Cataldo,Rachael L. Neve,Ying Jiang,Ying Jiang,Joanne Wuu,Moses V. Chao,Elliott J. Mufson,Ralph A. Nixon,Ralph A. Nixon,Shaoli Che,Shaoli Che +15 more
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TLDR
The hypothesis that neuronal endosomal dysfunction is associated with preclinical AD is supported and increased endocytic pathway activity, driven by elevated rab GTPase expression, may result in long-term deficits in hippocampal neurotrophic signaling and represent a key pathogenic mechanism underlying AD progression.About:
This article is published in Biological Psychiatry.The article was published on 2010-11-15 and is currently open access. It has received 240 citations till now. The article focuses on the topics: Endocytic cycle & Neurotrophin.read more
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Autophagy failure in Alzheimer's disease--locating the primary defect.
TL;DR: Current evidence strongly points to disruption of substrate proteolysis within autolysosomes for the principal mechanism underlying autophagy failure in AD, and attempts to restore more normal lysosomal proteolytic efficiency in mouse models of AD pathology have yielded promising therapeutic effects.
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Comparative lipidomic analysis of mouse and human brain with Alzheimer disease.
Robin B. Chan,Tiago Gil Oliveira,Etty Cortes,Lawrence S. Honig,Karen Duff,Scott A. Small,Markus R. Wenk,Guanghou Shui,Gilbert Di Paolo +8 more
TL;DR: In this paper, a system-based approach was employed to determine the lipidome of brain tissues affected by Alzheimer disease using liquid chromatography-mass spectrometry to profile extracts from the prefrontal cortex, entorhinal cortex, and cerebellum of late-onset AD patients.
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The endosomal-lysosomal system: from acidification and cargo sorting to neurodegeneration.
TL;DR: The endosomal-lysosomal system is emerging as a central player in a host of neurodegenerative diseases, demonstrating potential roles which are likely to be revealed in pathogenesis and for viable therapeutic strategies.
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Disorders of lysosomal acidification—The emerging role of v-ATPase in aging and neurodegenerative disease
TL;DR: The unique vulnerability of neurons to persistent low level lysosomal dysfunction is discussed and recent clinical and experimental studies that link dysfunction of the v-ATPase complex to neurodegenerative diseases across the age spectrum are reviewed.
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Amyloid-Independent Mechanisms in Alzheimer's Disease Pathogenesis
TL;DR: The studies showing how amyloid-independent mechanisms cause defective endo-lysosomal trafficking, altered intracellular signaling cascades, or impaired neurotransmitter release and contribute to synaptic dysfunction and/or neurodegeneration, leading to dementia in AD are summarized.
References
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Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease
Denise Harold,Richard Abraham,Paul Hollingworth,Rebecca Sims,Amy Gerrish,Marian L. Hamshere,Jaspreet Singh Pahwa,Valentina Moskvina,Kimberley Dowzell,Amy L. Williams,Nicola L. Jones,Charlene Thomas,Alexandra Stretton,Angharad R. Morgan,Simon Lovestone,John Powell,Petroula Proitsi,Michelle K. Lupton,Carol Brayne,David C. Rubinsztein,Michael Gill,Brian A. Lawlor,Aoibhinn Lynch,Kevin Morgan,Kristelle Brown,Peter Passmore,David Craig,Bernadette McGuinness,Stephen Todd,Clive Holmes,David M. A. Mann,A. David Smith,Seth Love,Patrick G. Kehoe,John Hardy,Simon Mead,Nick C. Fox,Martin N. Rossor,John Collinge,Wolfgang Maier,Frank Jessen,Britta Schürmann,Hendrik van den Bussche,Isabella Heuser,Johannes Kornhuber,Jens Wiltfang,Martin Dichgans,Lutz Frölich,Harald Hampel,Harald Hampel,Michael Hüll,Dan Rujescu,Alison Goate,John S. K. Kauwe,Carlos Cruchaga,Petra Nowotny,John C. Morris,Kevin Mayo,Kristel Sleegers,Karolien Bettens,Sebastiaan Engelborghs,Peter Paul De Deyn,Christine Van Broeckhoven,Gill Livingston,Nicholas Bass,Hugh Gurling,Andrew McQuillin,Rhian Gwilliam,Panagiotis Deloukas,Ammar Al-Chalabi,Christopher Shaw,Magda Tsolaki,Andrew B. Singleton,Rita Guerreiro,Thomas W. Mühleisen,Markus M. Nöthen,Susanne Moebus,Karl-Heinz Jöckel,Norman Klopp,H-Erich Wichmann,Minerva M. Carrasquillo,V. Shane Pankratz,Steven G. Younkin,Peter Holmans,Michael Conlon O'Donovan,Michael John Owen,Julie Williams +86 more
TL;DR: A two-stage genome-wide association study of Alzheimer's disease involving over 16,000 individuals, the most powerful AD GWAS to date, produced compelling evidence for association with Alzheimer's Disease in the combined dataset.
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Alzheimer's disease: cell-specific pathology isolates the hippocampal formation.
TL;DR: Examination of temporal lobe structures from Alzheimer patients reveals a specific cellular pattern of pathology of the subiculum of the hippocampal formation and layers II and IV of the entorhinal cortex that isolates the hippocampus from much of its input and output and probably contributes to the memory disorder in Alzheimer patients.
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Genome-wide association study indentifies variants at CLU and CR1 associated with Alzheimer’s disease
J-C Lambert,Simon Heath,G Even,Dominique Campion,K. Sleegers,Mikko Hiltunen,O Cambarros,Diana Zelenika,María J. Bullido,Béatrice Tavernier,Luc Letenneur,Karolien Bettens,Claudine Berr,Florence Pasquier,Nathalie Fievet,P Barbager-Gateau,S. Engelborghs,P.P. De Deyn,Ignacio Mateo,A Franck,Seppo Helisalmi,Elisa Porcellini,Olivier Hanon,M de Pancorbo,Corinne Lendon,Carole Dufouil,C Jaillard,Thierry Léveillard,Alvarez,Paolo Bosco,Michelangelo Mancuso,Francesco Panza,Benedetta Nacmias,Paola Bossù,Paola Piccardi,Giorgio Annoni,Davide Seripa,Daniela Galimberti,Didier Hannequin,Federico Licastro,Hilkka Soininen,Karen Ritchie,Hélène Blanché,J. F. Dartigues,Christophe Tzourio,Ivo Gut,Christine Van Broeckhoven,Annick Alpérovitch,P. Amouyel +48 more
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Erratum: Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer (Nature Genetics (2009) 41 (991-995))
Xifeng Wu,Yuanqing Ye,Lambertus A. Kiemeney,Patrick Sulem,Thorunn Rafnar,Giuseppe Matullo,Daniela Seminara,Teruhiko Yoshida,Norihisa Saeki,Angeline S. Andrew,Colin P.N. Dinney,Bogdan Czerniak,Zuo-Feng Zhang,Anne E. Kiltie,D. Timothy Bishop,Paolo Vineis,Stefano Porru,Frank Buntinx,Eliane Kellen,Maurice P. Zeegers,Rajesh Kumar,Peter Rudnai,Eugene Gurzau,Kvetoslava Koppova,Jose I. Mayordomo,Manuel Sanchez,Berta Saez,Annika Lindblom,Petra J. de Verdier,Gunnar Steineck,Gordon B. Mills,Alan R. Schned,Shen Chih Chang,Jie Lin,David W. Chang,Katherine S. Hale,Tadeusz Majewski,H. Barton Grossman,Steinunn Thorlacius,Unnur Thorsteinsdottir,Katja K.H. Aben,J. Alfred Witjes,Kari Stefansson,Christopher I. Amos,Margaret R. Karagas,Jian Gu +45 more
TL;DR: In the version of this article initially published online, Simonetta Guarrera and Silvia Polidoro were inadvertently omitted from the author list, and an affiliation was omitted for Paolo Vineis as mentioned in this paper.