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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Kuzuya, Akira; Zoltowska, Katarzyna M; Post, Kathryn L et al. (2016) Identification of the novel activity-driven interaction between synaptotagmin 1 and presenilin 1 links calcium, synapse, and amyloid beta. BMC Biol 14:25
Bolduc, David M; Montagna, Daniel R; Gu, Yongli et al. (2016) Nicastrin functions to sterically hinder γ-secretase-substrate interactions driven by substrate transmembrane domain. Proc Natl Acad Sci U S A 113:E509-18
Zhang, Jing; Lu, Dai; Wei, Han-Xun et al. (2016) Part 3: Notch-sparing γ-secretase inhibitors: SAR studies of 2-substituted aminopyridopyrimidinones. Bioorg Med Chem Lett 26:2138-41
Leriche, Geoffray; Chen, Allen C; Kim, Sumin et al. (2016) Fluorescent Analogue of Batimastat Enables Imaging of α-Secretase in Living Cells. ACS Chem Neurosci 7:40-5
Zoltowska, Katarzyna Marta; Maesako, Masato; Berezovska, Oksana (2016) Interrelationship between changes in the amyloid β 42/40 ratio and presenilin 1 conformation. Mol Med 22:
Bolduc, David M; Montagna, Daniel R; Seghers, Matthew C et al. (2016) The amyloid-beta forming tripeptide cleavage mechanism of γ-secretase. Elife 5:
Wei, Han-Xun; Lu, Dai; Sun, Vivien et al. (2016) Part 2. Notch-sparing γ-secretase inhibitors: The study of novel γ-amino naphthyl alcohols. Bioorg Med Chem Lett 26:2133-7
Lu, Dai; Wei, Han-Xun; Zhang, Jing et al. (2016) Part 1: Notch-sparing γ-secretase inhibitors: The identification of novel naphthyl and benzofuranyl amide analogs. Bioorg Med Chem Lett 26:2129-32
Selkoe, Dennis J; Hardy, John (2016) The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med 8:595-608
D'Avanzo, Carla; Aronson, Jenna; Kim, Young Hye et al. (2015) Alzheimer's in 3D culture: challenges and perspectives. Bioessays 37:1139-48

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