Maria Clara Selles, Juliana T.S. Fortuna, Magali C. Cercato, Luis Eduardo Santos, Luciana Domett, Andre L.B. Bitencourt, Mariane Favero Carraro, Amanda S. Souza, Helena Janickova, Caroline Vieira Azevedo, Henrique Correia Campos, Jorge M. de Souza, Soniza Alves-Leon, Vania F. Prado, Marco A.M. Prado, Alberto L. Epstein, Anna Salvetti, Beatriz Monteiro Longo, Ottavio Arancio, William L. Klein, Adriano Sebollela, Fernanda G. De Felice, Diana A. Jerusalinsky, Sergio T. Ferreira, New York University School of Medicine (NYU Grossman School of Medicine), Universidade Federal do Rio de Janeiro (UFRJ), Universidad de Buenos Aires [Buenos Aires] (UBA), Universidade de São Paulo = University of São Paulo (USP), University of Western Ontario (UWO), Universidade Federal de São Paulo, Hospital Universitário Clementino Fraga Filho [Rio de Janeiro] (HUCFF / UFRJ), Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Columbia University [New York], Northwestern University [Evanston], Queen's University [Kingston, Canada], 16/820,269, Northwestern University, NU, Canadian Institutes of Health Research, IRSC: PJT 159781, PJT 162431, Alzheimer Society, Fundação de Amparo à Pesquisa do Estado de São Paulo, FAPESP: 2014/25681-3, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES, Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET, Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, FAPERJ, Instituto Nacional de Ciência e Tecnologia de Neurociência Translacional, INCT-INNT, International Society for Neurochemistry, ISN, S.T.F. and F.G.D.F. were supported by grants from the National Council for Scientific and Technological Development (CNPq/Brazil), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ/Brazil), and National Institute of Translational Neuroscience (Brazil). S.T.F. and D.A.J. were jointly supported by a binational research grant from CNPq/CONICET. A. Sebollela was supported by the São Paulo Research Foundation (FAPESP) grant 2014/25681-3 . M.A.M.P. and V.F.P. received support from the Alzheimer’s Society of Canada and the Canadian Institutes of Health Research (CIHR, PJT 162431 and PJT 159781 ). A.L.B.B. received a predoctoral fellowship from CNPq. M.C.S. received predoctoral fellowships from CNPq and FAPERJ and travel grants from the International Society for Neurochemistry , Company of Biologists , and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior . We thank Drs. Moses Chao and Mauricio M. Oliveira for critical reading of the manuscript and discussions., S.T.F. and F.G.D.F. were supported by grants from the National Council for Scientific and Technological Development (CNPq/Brazil), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ/Brazil), and National Institute of Translational Neuroscience (Brazil). S.T.F. and D.A.J. were jointly supported by a binational research grant from CNPq/CONICET. A. Sebollela was supported by the São Paulo Research Foundation (FAPESP) grant 2014/25681-3. M.A.M.P. and V.F.P. received support from the Alzheimer's Society of Canada and the Canadian Institutes of Health Research (CIHR, PJT 162431 and PJT 159781). A.L.B.B. received a predoctoral fellowship from CNPq. M.C.S. received predoctoral fellowships from CNPq and FAPERJ and travel grants from the International Society for Neurochemistry, Company of Biologists, and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. We thank Drs. Moses Chao and Mauricio M. Oliveira for critical reading of the manuscript and discussions. M.C.S. D.A.J. and S.T.F. designed the study. A. Sebollela, W.L.K. and S.T.F. developed the recombinant NUsc1 scFv. D.A.J. A.L.E. A. Salvetti, and S.T.F. conceived constructs and vector development. M.C.S. J.T.S.F. M.C.C. L.E.S. L.D. A.L.B.B. M.F.C. A.S.S. H.J. C.V.A. and H.C.C. performed research. M.C.S. J.T.S.F. M.C.C. L.E.S. L.D. A.L.B.B. O.A. F.G.D.F. and S.T.F analyzed data. J.M.S. S.A.L. V.F.P. M.A.M.P. A.L.E. A. Salvetti, A. Sebollela, and W.L.K. contributed reagents, materials, and analysis tools. M.C.S. J.T.S.F. L.E.S. A.L.E. A. Salvetti, A. Sebollela, B.M.L, O.A. W.L.K. F.G.D.F. D.A.J. and S.T.F. analyzed and discussed the results. M.C.S. W.L.K. and S.T.F. wrote the manuscript with contributions from other authors. A patent application covering the use of AAV-NUsc1 in Alzheimer's disease has been filed with the USPTO (16/820,269, and pending) by Northwestern University with S.T.F. W.L.K. D.A.J. A. Sebollela, and M.C.S. as named inventors.