Icahn School of Medicine at Mount Sinai has received a USD 1.21 million NIH R01 grant to test whether blocking follicle-stimulating hormone (FSH) can reduce Alzheimer's-like pathology in mouse models of Down syndrome, a population in which nearly all individuals develop Alzheimer's dementia by age 60. The award, issued by the National Institute on Aging under an NIH Office of the Director initiative (RFA-OD-22-009), continues work led by principal investigators Mone Zaidi and Ki Ann Goosens at Mount Sinai.
The project builds on the investigators' prior finding that elevated FSH accelerates amyloid pathology in standard Alzheimer's mouse models. The team will now measure FSH levels across the lifespan in two Down syndrome mouse models and test a first-in-class humanized monoclonal antibody that blocks FSH receptor signaling, administered late in life to assess effects on amyloid accumulation, cognition, and FSH-linked comorbidities such as bone loss and metabolic dysfunction. The approach reframes Alzheimer's risk in Down syndrome as partly endocrine-driven rather than solely a consequence of amyloid precursor protein triplication from chromosome 21.
No FSH-targeted antibody has reached clinical testing for Alzheimer's disease, distinguishing this program from amyloid- and tau-directed antibodies such as lecanemab (Leqembi) and donanemab (Kisunla), which do not address endocrine contributions to neurodegeneration. The work remains preclinical, with efficacy and safety confined to mouse models through the project's 2030 end date.