@article{23ec1019a5ba4d8b93e7560b75468aff,
title = "FSH blockade improves cognition in mice with Alzheimer{\textquoteright}s disease",
abstract = "Alzheimer{\textquoteright}s disease has a higher incidence in older women, with a spike in cognitive decline that tracks with visceral adiposity, dysregulated energy homeostasis and bone loss during the menopausal transition1,2. Inhibiting the action of follicle-stimulating hormone (FSH) reduces body fat, enhances thermogenesis, increases bone mass and lowers serum cholesterol in mice3–7. Here we show that FSH acts directly on hippocampal and cortical neurons to accelerate amyloid-β and Tau deposition and impair cognition in mice displaying features of Alzheimer{\textquoteright}s disease. Blocking FSH action in these mice abrogates the Alzheimer{\textquoteright}s disease-like phenotype by inhibiting the neuronal C/EBPβ–δ-secretase pathway. These data not only suggest a causal role for rising serum FSH levels in the exaggerated Alzheimer{\textquoteright}s disease pathophysiology during menopause, but also reveal an opportunity for treating Alzheimer{\textquoteright}s disease, obesity, osteoporosis and dyslipidaemia with a single FSH-blocking agent.",
author = "Jing Xiong and Kang, {Seong Su} and Zhihao Wang and Xia Liu and Kuo, {Tan Chun} and Funda Korkmaz and Ashley Padilla and Sari Miyashita and Pokman Chan and Zhaohui Zhang and Pavel Katsel and Jocoll Burgess and Anisa Gumerova and Kseniia Ievleva and Damini Sant and Yu, {Shan Ping} and Valeriia Muradova and Tal Frolinger and Daria Lizneva and Jameel Iqbal and Goosens, {Ki A.} and Sakshi Gera and Rosen, {Clifford J.} and Vahram Haroutunian and Vitaly Ryu and Tony Yuen and Mone Zaidi and Keqiang Ye",
note = "Funding Information: This work performed at Emory University School of Medicine was supported by NIH grants RF1 AG051538 and R01 AG065177 to K.Y. K.Y. thanks the staff at the Alzheimer{\textquoteright}s Disease Research Center at Emory University for human samples; the Rodent Behavioral Core (RBC), one of the Emory Integrated Core Facilities; the Viral Vector Core of the Emory Neuroscience NINDS Core Facility (P30 NS055077); and the NIH{\textquoteright}s Georgia Clinical and Translational Science Alliance (UL1 TR002378). Work at Icahn School of Medicine at Mount Sinai performed at the Center for Translational Medicine and Pharmacology (CeTMaP) was supported by U19 AG060917 to M.Z. and C.J.R.; R01 DK113627 to M.Z. and J.I.; and R01 AG071870, R01 AG074092 and U01 AG073148 to T.Y. and M.Z. M.Z. thanks the Harrington Discovery Institute for the Innovator–Scholar Award towards development of the FSH-Ab. C.J.R. acknowledges support from the NIH (P20 GM121301 to C.J.R.). We thank M. Ehrlich and S. Gandy for their intellectual contributions, and S. Babunovic for proofreading the final version of the paper. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2022",
month = mar,
day = "17",
doi = "10.1038/s41586-022-04463-0",
language = "English",
volume = "603",
pages = "470--476",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7901",
}