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FSH blockade improves cognition in mice with Alzheimer’s disease

Author

Listed:
  • Jing Xiong

    (Emory University School of Medicine
    Renmin Hospital of Wuhan University)

  • Seong Su Kang

    (Emory University School of Medicine)

  • Zhihao Wang

    (Emory University School of Medicine)

  • Xia Liu

    (Emory University School of Medicine)

  • Tan-Chun Kuo

    (Icahn School of Medicine at Mount Sinai)

  • Funda Korkmaz

    (Icahn School of Medicine at Mount Sinai)

  • Ashley Padilla

    (Icahn School of Medicine at Mount Sinai)

  • Sari Miyashita

    (Icahn School of Medicine at Mount Sinai)

  • Pokman Chan

    (Alamak Biosciences)

  • Zhaohui Zhang

    (Renmin Hospital of Wuhan University)

  • Pavel Katsel

    (Icahn School of Medicine at Mount Sinai)

  • Jocoll Burgess

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Anisa Gumerova

    (Icahn School of Medicine at Mount Sinai)

  • Kseniia Ievleva

    (Icahn School of Medicine at Mount Sinai)

  • Damini Sant

    (Icahn School of Medicine at Mount Sinai)

  • Shan-Ping Yu

    (Emory University School of Medicine)

  • Valeriia Muradova

    (Icahn School of Medicine at Mount Sinai)

  • Tal Frolinger

    (Icahn School of Medicine at Mount Sinai)

  • Daria Lizneva

    (Icahn School of Medicine at Mount Sinai)

  • Jameel Iqbal

    (Icahn School of Medicine at Mount Sinai)

  • Ki A. Goosens

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Sakshi Gera

    (Icahn School of Medicine at Mount Sinai)

  • Clifford J. Rosen

    (Maine Medical Center Research Institute)

  • Vahram Haroutunian

    (Icahn School of Medicine at Mount Sinai)

  • Vitaly Ryu

    (Icahn School of Medicine at Mount Sinai)

  • Tony Yuen

    (Icahn School of Medicine at Mount Sinai)

  • Mone Zaidi

    (Icahn School of Medicine at Mount Sinai)

  • Keqiang Ye

    (Emory University School of Medicine
    Chinese Academy of Sciences)

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.

Suggested Citation

  • 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 & Kse, 2022. "FSH blockade improves cognition in mice with Alzheimer’s disease," Nature, Nature, vol. 603(7901), pages 470-476, March.
  • Handle: RePEc:nat:nature:v:603:y:2022:i:7901:d:10.1038_s41586-022-04463-0
    DOI: 10.1038/s41586-022-04463-0
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    Cited by:

    1. Andrew E. Warfield & Pooja Gupta & Madison M. Ruhmann & Quiana L. Jeffs & Genevieve C. Guidone & Hannah W. Rhymes & McKenzi I. Thompson & William D. Todd, 2023. "A brainstem to circadian system circuit links Tau pathology to sundowning-related disturbances in an Alzheimer’s disease mouse model," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Jia Duan & Peiyu Xu & Huibing Zhang & Xiaodong Luan & Jiaqi Yang & Xinheng He & Chunyou Mao & Dan-Dan Shen & Yujie Ji & Xi Cheng & Hualiang Jiang & Yi Jiang & Shuyang Zhang & Yan Zhang & H. Eric Xu, 2023. "Mechanism of hormone and allosteric agonist mediated activation of follicle stimulating hormone receptor," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. Yiyuan Xia & Yifan Xiao & Zhi-Hao Wang & Xia Liu & Ashfaqul M. Alam & John P. Haran & Beth A. McCormick & Xiji Shu & Xiaochuan Wang & Keqiang Ye, 2023. "Bacteroides Fragilis in the gut microbiomes of Alzheimer’s disease activates microglia and triggers pathogenesis in neuronal C/EBPβ transgenic mice," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. Yi Cheng & Hong Zhu & Jun Ren & Hai-Yan Wu & Jia-En Yu & Lu-Yang Jin & Hai-Yan Pang & Hai-Tao Pan & Si-Si Luo & Jing Yan & Kai-Xuan Dong & Long-Yun Ye & Cheng-Liang Zhou & Jie-Xue Pan & Zhuo-Xian Meng, 2023. "Follicle-stimulating hormone orchestrates glucose-stimulated insulin secretion of pancreatic islets," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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