FSH blockade improves cognition in mice with Alzheimer's disease

Article

关键词: BINDING-PROTEIN-BETA;    PREVENTS BONE LOSS;    LUTEINIZING-HORMONE;    BLOCKING ANTIBODY;    C/EBP-BETA;    DEMENTIA;    WOMEN;    GONADOTROPIN;    MEMORY;    GENE;   

DOI  :  10.1038/s41586-022-04463-0

来源: SCIE

【 摘 要 】

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 transition(1,2). Inhibiting the action of follicle-stimulating hormone (FSH) reduces body fat, enhances thermogenesis, increases bone mass and lowers serum cholesterol in mice(3-7). Here we show that FSH acts directly on hippocampal and cortical neurons to accelerate amyloid-beta and Tau deposition and impair cognition in mice displaying features ofAlzheimer's disease. Blocking FSH action in these mice abrogates the Alzheimer's disease-like phenotype by inhibiting the neuronal C/EBP beta-delta-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.

【 授权许可】

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