| Literature DB >> 35236988 |
Jing Xiong1,2, Seong Su Kang1, Zhihao Wang1, Xia Liu1, Tan-Chun Kuo3, Funda Korkmaz3, Ashley Padilla3, Sari Miyashita3, Pokman Chan4, Zhaohui Zhang2, Pavel Katsel5, Jocoll Burgess3,5, Anisa Gumerova3, Kseniia Ievleva3, Damini Sant3, Shan-Ping Yu6, Valeriia Muradova3, Tal Frolinger3, Daria Lizneva3, Jameel Iqbal3, Ki A Goosens3,5, Sakshi Gera3, Clifford J Rosen7, Vahram Haroutunian5, Vitaly Ryu3, Tony Yuen3, Mone Zaidi8, Keqiang Ye9,10.
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.Entities:
Mesh：
Substances：
Year: 2022 PMID： 35236988 DOI： 10.1038/s41586-022-04463-0
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 69.504