The Administrative and Educational Core will continue to play a key role in the program, integrating the activities of this highly interactive consortium of 4 independent labs and 3 core units (comprised of more than 25 scientific personnel) at the Massachusetts General Hospital and Brigham and Women's Hospital. The 10 co-investigators of the program are strongly committed to enhancing scientific collaboration, communication and education, as we have done during the two preceeding terms of this Program. In this regard, we have found the three specific forums proposed in this core to have been highly effective tools in the previous funding periods. They are therefore included in this renewal of Core A as a means of achieving the important goals of scientific cooperation and exchange that define a NIH Pogram Project Grant. 1) Regularly scheduled Project Leaders'Meetings, attended by all the Project Pi's, their coinvesigators, the Leaders of Core B and C and and selected project scientists, provide ongoing opportunities to examine new developments in each of the 4 projects, and to review one or more of the projects in depth at each meeting, with analysis of progress and problems. 2) Our superb Scientific Advisory Board will continue to consult with the program scientists on an ad hoc basis throughout the year and then convene for an intensive annual on-site review of major new developments in each of the projects. 3) Our successful Seminar Series """"""""Basic and Applied Biology Relevant to Neurodegeneration"""""""" will soon enter its 9th year, presenting local and out-of-town speakers, including our own investigators, who inform the Program members and the Boston scientific community at large of new developments in presenilin biology, the pathogenesis of AD and numberous relevant basic research issues. In addition to running the program's vital educational and information-sharing activities, Core A will, as before, manage all the day-to-day fiscal and administrative issues related to our large multi-site program, including regular income/expense reports, inter-institutional personnel and reagent exchanges, joint publications, regular exchange of all publications emanting from the grant, preparation of non-competing renewal applications, and timely and efficient communication with the National Institute on Aging.

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Zoltowska, Katarzyna Marta; Berezovska, Oksana (2017) Dynamic Nature of presenilin1/?-Secretase: Implication for Alzheimer's Disease Pathogenesis. Mol Neurobiol :
Gong, Yi; Sasidharan, Nikhil; Laheji, Fiza et al. (2017) Microglial dysfunction as a key pathological change in adrenomyeloneuropathy. Ann Neurol 82:813-827
Kara, Eleanna; Marks, Jordan D; Fan, Zhanyun et al. (2017) Isoform- and cell type-specific structure of apolipoprotein E lipoparticles as revealed by a novel Forster resonance energy transfer assay. J Biol Chem 292:14720-14729
Raven, Frank; Ward, Joseph F; Zoltowska, Katarzyna M et al. (2017) Soluble Gamma-secretase Modulators Attenuate Alzheimer's ?-amyloid Pathology and Induce Conformational Changes in Presenilin 1. EBioMedicine 24:93-101
Wagner, Steven L; Rynearson, Kevin D; Duddy, Steven K et al. (2017) Pharmacological and Toxicological Properties of the Potent Oral ?-Secretase Modulator BPN-15606. J Pharmacol Exp Ther 362:31-44
Yang, Ting; Li, Shaomin; Xu, Huixin et al. (2017) Large Soluble Oligomers of Amyloid ?-Protein from Alzheimer Brain Are Far Less Neuroactive Than the Smaller Oligomers to Which They Dissociate. J Neurosci 37:152-163
Ward, Joseph; Wang, Haizhi; Saunders, Aleister J et al. (2017) Mechanisms that synergistically regulate ?-secretase processing of APP and A?-? protein levels: relevance to pathogenesis and treatment of Alzheimer's disease. Discov Med 23:121-128
Zoltowska, Katarzyna Marta; Maesako, Masato; Lushnikova, Iryna et al. (2017) Dynamic presenilin 1 and synaptotagmin 1 interaction modulates exocytosis and amyloid ? production. Mol Neurodegener 12:15
Bolduc, D M; Selkoe, D J; Wolfe, M S (2017) Enzymatic Assays for Studying Intramembrane Proteolysis. Methods Enzymol 584:295-308
Williamson, Rebecca L; Laulagnier, Karine; Miranda, André M et al. (2017) Disruption of amyloid precursor protein ubiquitination selectively increases amyloid ? (A?) 40 levels via presenilin 2-mediated cleavage. J Biol Chem 292:19873-19889

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