Faculty Articles

Document Type

Article

Publication Date

8-9-2023

Publication Title

Biology of Sex Differences

ISSN or ISBN

2042-6410

Volume

14

Issue/Number

51

ISSN

2042-6410

Abstract/Excerpt

BACKGROUND: Alzheimer's disease (AD) is notably associated with cognitive decline resulting from impaired function of hippocampal and cortical areas; however, several other domains and corresponding brain regions are affected. One such brain region is the hypothalamus, shown to atrophy and develop amyloid and tau pathology in AD patients. The hypothalamus controls several functions necessary for survival, including energy and glucose homeostasis. Changes in appetite and body weight are common in AD, often seen several years prior to the onset of cognitive symptoms. Therefore, altered metabolic processes may serve as a biomarker for AD, as well as a target for treatment, considering they are likely both a result of pathological changes and contributor to disease progression. Previously, we reported sexually dimorphic metabolic disturbances in ~ 7-month-old 3xTg-AD mice, accompanied by differences in systemic and hypothalamic inflammation.

METHODS: In the current study, we investigated metabolic outcomes and hypothalamic inflammation in 3xTg-AD males and females at 3, 6, 9, and 12 months of age to determine when these sex differences emerge.

RESULTS: In agreement with our previous study, AD males displayed less weight gain and adiposity, as well as reduced blood glucose levels following a glucose challenge, compared to females. These trends were apparent by 6-9 months of age, coinciding with increased expression of inflammatory markers (Iba1, GFAP, TNF-α, and IL-1β) in the hypothalamus of AD males.

CONCLUSIONS: These findings provide additional evidence for sex-dependent effects of AD pathology on energy and glucose homeostasis, which may be linked to hypothalamic inflammation.

DOI

10.1186/s13293-023-00536-5

ORCID ID

0000-0002-5110-9183

Comments

Acknowledgements Thank you to Nathan Albert, Melissa Thomas, Alvira Tyagi, and Allegra Wu for assistance with tissue collection.

Funding This work was funded by NINDS F31 NS115290 (OJG), NINDS/NIA R01NS110749 (KLZ), NIA U01AG072464 (KLZ), Albany Medical College startup funds, American Heart Association 946666 (LSR), NINDS R16NS134540-01 (LSR), NIA R03AG081865-01 (LSR).

© The Author(s) 2023.

PubMed ID

37559092

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Peer Reviewed

Included in

Psychology Commons

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