# FSH - An Aging Hormone?

> **NIH NIH U19** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $407,765

## Abstract

PROJECT SUMMARY
Alzheimer’s disease, a crippling disease of the aging polulation, shows a predilection for women, particularly
after menopause . The biological basis of the higher incidence, more rapid progression, and enhanced
symptom load in post–menopausal women, when compared with men of the same age, remains unclear.
Declining estrogen levels have been implicated, but studies showing an early spike in incidence of Alzheimer’s
neuropathology and cognitive impairment at a time when estrogen levels are relatively unperturbed makes this
1-5
possibility unlikely
6-12
. It is also notable that FSH levels rise during this perimenopausal phase, and changes in
serum FSH have been implicated by us and others in the bone loss, visceral adiposity, and dysregulated energy
metabolism that ensue8,9,13-16. Indeed, contrary to textbook physiology, wherein pituitary hormones, such as
FSH, were assigned a single regulatory function, we discovered more ubiquitous actions of almost every pituitary
hormone16-22. We have identified functional FSH receptors (FSHRs) on bone cells and adipocytes13,18, and, in
preliminary data provided here, report receptors in several brain regions. In collaborative studies with Dr.
Keqiang Ye (Emory), we also show that FSH given to 3xTg mice worsens the Alzheimer’s neuropathology and
cognitive decline, and importantly, that our polyclonal antibody to a defined receptor–binding region of FSHβ
attenuates these changes. The question therefore is whether actions of FSH on the brain can contribute to
cognitive deterioration, particularly when FSH levels are elevated. This question is in contextual alignment with
U19 AG60917, in which we explore the actions of FSH, as an aging hormone, on bone and fat, as well as with
PA–18–591 (NOT–AG–20–008), that seeks to extend the overall relevance of this work to Alzheimer’s disease.
Thus, our goal for this yearlong supplement is to solidify our current preliminary data on the expression of FSHRs
in brain regions (Specific Aim 1), contemporaneously reproduce neuropathological and behavioral datasets from
the Emory lab that utilized our polyclonal anti–FSHβ antibody, and examine the effect of our newly–developed
humanized monoclonal antibody, Finskelzumab, in the 3xTg mouse (Specific Aim 2). Noting that Finskelzumab
is currently in preclinical development for use in osteoporosis and obesity, it would be a monumental success
story if its use could be extended to Alzheimer’s disease. Whether or not this is possible, we expect any new
data to form the framework for a future R01 to probe the neural functions of FSH.

## Key facts

- **NIH application ID:** 10123527
- **Project number:** 3U19AG060917-02S1
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** CLIFFORD JAMES ROSEN
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $407,765
- **Award type:** 3
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123527

## Citation

> US National Institutes of Health, RePORTER application 10123527, FSH - An Aging Hormone? (3U19AG060917-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10123527. Licensed CC0.

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