Neuroendocrinology and Pituitary

SUN-089 - Fshr Gene Depletion Prevents Recognition Memory Loss, Fat Accrual and Bone Loss in Alzheimer'S Mice

Sunday, June 14, 2026

9:00 AM - 4:00 PM CT

Location: ENDOExpo; Poster Floor

Abstract Poster Presenter(s)

UC

Uliana Cheliadinova, MD

Instructor
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
New York, NY, United States

Co-Author(s)

Steven Sims, MS (he/him/his)

Institute for Translational Medicine and Pharmacology
Icahn School of Medicine at Mount Sinai
New York, NY, United States
Funda Korkmaz, MD

Medical Resident
Jersey City Medical Center - Open School - Open School
West New York, NJ, United States
DV

Darya Vasilyeva, MD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
VL

Victoria Laurencin, BS

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
JG

Judit Gimenez-Roig, MSc

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, New York, United States
GP

Georgii Pevnev, MD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
GB

Guzel Burganova, MD PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
ZT

Zehra Tumoglu, M.D.

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, NY, New York, United States
SP

Surabhi Parte, BS (she/her/hers)

Associate Researcher
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
Jersey City, NJ, United States
FS

Farhath Sultana, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
AP

Anusha Pallapati, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, New York, United States
Satish Rojekar, PhD

Assistant Professor
Icahn School of Medicine at Mount Sinai
Jersey City, NJ, United States
AM

Anne Macdonald, BA

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
SH

Susan Hutchison, BS

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
AS

Avi Soussan, BS

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, New York, United States
YW

Yi Wei, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, New York, United States
OM

Ofer Moldavski, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, NY, New York, United States
AG

Anisa Gumerova, MD, PhD (she/her/hers)

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, NY, New York, United States
WZ

Weibin Zhou, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York City, New York, United States
OB

Orly Barak, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
KG

Ki Goosens, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, NY, New York, United States
Vitaly Ryu, Ph.D. (he/him/his)

Associate Professor
Mount Sinai
New York, NY, United States
DL

Daria Lizneva, MD, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
Clifford J. Rosen, MD

Director Clinical & Translational Medicine
Maine Medical Center Research Institute
Scarborough, ME, United States
TY

Tony Yuen, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
TF

Tal Frolinger, PhD (she/her/hers)

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, NY, New York, United States

Senior Author/Primary Investigator(s)

MZ

Mone Zaidi, MD, PhD (he/him/his)

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, NY, New York, United States

Disclosure(s):

Uliana Cheliadinova, MD: No financial relationships to disclose

Steven Sims, MS: No financial relationships to disclose

Funda Korkmaz, MD: No financial relationships to disclose

Satish Rojekar, PhD: No financial relationships to disclose

Vitaly Ryu, PhD: No financial relationships to disclose

Epidemiologic evidence links follicle-stimulating hormone (FSH), a pituitary glycoprotein that rises during menopause, to memory loss, fat accumulation, and bone loss. We and others have shown that the attenuation of FSH signaling, either genetically or pharmacologically, prevents memory loss, fat accrual, and bone loss in multiple mouse models. Here, we investigated whether the genetic depletion of the FSH receptor (Fshr) affects recognition memory, body composition, and bone mineral density (BMD) in two AD mouse models. We generated male and female 3xTg and APP-KI mice carrying the Fshr+/+, Fshr+/–, and Fshr–/– genotypes. Recognition and spatial memory were evaluated using Novel Object Recognition (NOR) and Morris Water Maze (MWM) tests, respectively, at 5–6 months and 8–12 months. Body composition (fat, lean, and total mass) and site-specific bone mineral density (femur, tibia, L3–L5 spine) measurements were made using quantitative nuclear magnetic resonance (qNMR) and dual-energy X-ray absorptiometry (DXA), respectively, at 6 and 12 months. Given that female Fshr–/– genotypes are otherwise hypogonadal, they were implanted with 17β-estradiol pellets at 8–12 weeks of age to normalize serum estrogen. Impaired spatial memory (MWM) was found in 3xTg;Fshr+/+ mice at 5 months of age. The loss of memory acquisition and retrieval were both rescued in 3xTg;Fshr–/– mice and, to a lesser extent, in 3xTg;Fshr+/– mice, documenting clear gene-dose-dependent prevention of spatial memory loss. Furthermore, at 5 and 8 months, sham-operated 3xTg;Fshr–/– mice showed better memory performance during the learning and/or retrieval phases, further suggesting that Fshr deletion prevents age-related progression of memory deficits. This prevention was not seen when mice were ovariectomized, except in the 8-month-old 3xTg;Fshr–/– mice. There was also a gene-dose-dependent reduction mainly in the amyloid β40 isoform in whole brain extracts. In addition, the deficit in recognition memory (NOR) at 6 months was rescued in female 3xTg;Fshr–/– and APP-KI;Fshr–/– mice, but not in male mice. Likewise, female, but not male 3xTg;Fshr–/– mice showed reduced fat mass at both 6 and 12 months, but without changes in total body mass. In contrast, in the APP-KI cohort, both female and male Fshr–/– mice showed reduced fat mass at 6, but not at 12 months. DXA revealed that female, but not male APP-KI;Fshr–/– mice showed progressive increases with time in BMDs in tibiae, femora, and vertebrae, which were either statistically significant or approached significance. This phenotype was not observed on the 3xTg background. These studies constitute the first report for time- and strain-dependent effects of global Fshr depletion in the same mouse, setting the stage for the simultaneous prevention, using a single therapeutic, of three disorders of public health magnitude-Alzheimer's disease, obesity and osteoporosis.

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