@article{824c90383f384369a751b5ff0efc8b46,
title = "A brain proteomic signature of incipient Alzheimer's disease in young APOE ε4 carriers identifies novel drug targets",
abstract = "Aptamer-based proteomics revealed differentially abundant proteins in Alzheimer's disease (AD) brains in the Baltimore Longitudinal Study of Aging and Religious Orders Study (mean age, 89 ± 9 years). A subset of these proteins was also differentially abundant in the brains of young APOE ε4 carriers relative to noncarriers (mean age, 39 ± 6 years). Several of these proteins represent targets of approved and experimental drugs for other indications and were validated using orthogonal methods in independent human brain tissue samples as well as in transgenic AD models. Using cell culture-based phenotypic assays, we showed that drugs targeting the cytokine transducer STAT3 and the Src family tyrosine kinases, YES1 and FYN, rescued molecular phenotypes relevant to AD pathogenesis. Our findings may accelerate the development of effective interventions targeting the earliest molecular triggers of AD.",
author = "Roberts, {Jackson A.} and Varma, {Vijay R.} and Yang An and Sudhir Varma and Juli{\'a}n Candia and Giovanna Fantoni and Vinod Tiwari and Carlos Anerillas and Andrew Williamson and Atsushi Saito and Tina Loeffler and Irene Schilcher and Ruin Moaddel and Mohammed Khadeer and Jacqueline Lovett and Toshiko Tanaka and Olga Pletnikova and Troncoso, {Juan C.} and Bennett, {David A.} and Albert, {Marilyn S.} and Kaiwen Yu and Mingming Niu and Vahram Haroutunian and Bin Zhang and Junmin Peng and Croteau, {Deborah L.} and Resnick, {Susan M.} and Myriam Gorospe and Bohr, {Vilhelm A.} and Luigi Ferrucci and Madhav Thambisetty",
note = "Funding Information: This work was supported by NIH grants P30AG10161 (D.A.B.), R01AG15819 (D.A.B.), R01AG053987 (B.Z. and V.H.), U01AG046170 (B.Z. and V.H.), and RF1AG057440 (B.Z. and V.H.); Andrew and Lillian A. Posey Foundation (M.T.); and Intramural Research Program of the NIH, National Institute on Aging (M.T.) Publisher Copyright: Copyright {\textcopyright} 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).",
year = "2021",
month = nov,
doi = "10.1126/sciadv.abi8178",
language = "English",
volume = "7",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "46",
}