FSH blockade improves cognition in mice with Alzheimer’s disease

Jing Xiong, Seong Su Kang, Zhihao Wang, Xia Liu, Tan Chun Kuo, Funda Korkmaz, Ashley Padilla, Sari Miyashita, Pokman Chan, Zhaohui Zhang, Pavel Katsel, Jocoll Burgess, Anisa Gumerova, Kseniia Ievleva, Damini Sant, Shan Ping Yu, Valeriia Muradova, Tal Frolinger, Daria Lizneva, Jameel IqbalKi A. Goosens, Sakshi Gera, Clifford J. Rosen, Vahram Haroutunian, Vitaly Ryu, Tony Yuen, Mone Zaidi, Keqiang Ye

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Alzheimer’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’s disease. Blocking FSH action in these mice abrogates the Alzheimer’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’s disease pathophysiology during menopause, but also reveal an opportunity for treating Alzheimer’s disease, obesity, osteoporosis and dyslipidaemia with a single FSH-blocking agent.

Original languageEnglish
Pages (from-to)470-476
Number of pages7
JournalNature
Volume603
Issue number7901
DOIs
StatePublished - 17 Mar 2022

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