N-acetylneuraminic acid links immune exhaustion and accelerated memory deficit in diet-induced obese Alzheimer’s disease mouse model

Stefano Suzzi (), Tommaso Croese, Adi Ravid, Or Gold, Abbe R. Clark, Sedi Medina, Daniel Kitsberg, Miriam Adam, Katherine A. Vernon, Eva Kohnert, Inbar Shapira, Sergey Malitsky, Maxim Itkin, Alexander Brandis, Tevie Mehlman, Tomer M. Salame, Sarah P. Colaiuta, Liora Cahalon, Michal Slyper, Anna Greka (), Naomi Habib () and Michal Schwartz ()
Additional contact information
Stefano Suzzi: Weizmann Institute of Science, Department of Brain Sciences
Tommaso Croese: Weizmann Institute of Science, Department of Brain Sciences
Adi Ravid: The Hebrew University of Jerusalem, Edmond & Lily Safra Center for Brain Sciences
Or Gold: The Hebrew University of Jerusalem, Edmond & Lily Safra Center for Brain Sciences
Abbe R. Clark: Broad Institute of MIT and Harvard
Sedi Medina: Weizmann Institute of Science, Department of Brain Sciences
Daniel Kitsberg: The Hebrew University of Jerusalem, Edmond & Lily Safra Center for Brain Sciences
Miriam Adam: The Hebrew University of Jerusalem, Edmond & Lily Safra Center for Brain Sciences
Katherine A. Vernon: Broad Institute of MIT and Harvard
Eva Kohnert: Broad Institute of MIT and Harvard
Inbar Shapira: The Hebrew University of Jerusalem, Edmond & Lily Safra Center for Brain Sciences
Sergey Malitsky: Weizmann Institute of Science, Life Sciences Core Facilities
Maxim Itkin: Weizmann Institute of Science, Life Sciences Core Facilities
Alexander Brandis: Weizmann Institute of Science, Life Sciences Core Facilities
Tevie Mehlman: Weizmann Institute of Science, Life Sciences Core Facilities
Tomer M. Salame: Weizmann Institute of Science, Life Sciences Core Facilities
Sarah P. Colaiuta: Weizmann Institute of Science, Department of Brain Sciences
Liora Cahalon: Weizmann Institute of Science, Department of Brain Sciences
Michal Slyper: Broad Institute of MIT and Harvard
Anna Greka: Broad Institute of MIT and Harvard
Naomi Habib: The Hebrew University of Jerusalem, Edmond & Lily Safra Center for Brain Sciences
Michal Schwartz: Weizmann Institute of Science, Department of Brain Sciences

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract Systemic immunity supports lifelong brain function. Obesity posits a chronic burden on systemic immunity. Independently, obesity was shown as a risk factor for Alzheimer’s disease (AD). Here we show that high-fat obesogenic diet accelerated recognition-memory impairment in an AD mouse model (5xFAD). In obese 5xFAD mice, hippocampal cells displayed only minor diet-related transcriptional changes, whereas the splenic immune landscape exhibited aging-like CD4+ T-cell deregulation. Following plasma metabolite profiling, we identified free N-acetylneuraminic acid (NANA), the predominant sialic acid, as the metabolite linking recognition-memory impairment to increased splenic immune-suppressive cells in mice. Single-nucleus RNA-sequencing revealed mouse visceral adipose macrophages as a potential source of NANA. In vitro, NANA reduced CD4+ T-cell proliferation, tested in both mouse and human. In vivo, NANA administration to standard diet-fed mice recapitulated high-fat diet effects on CD4+ T cells and accelerated recognition-memory impairment in 5xFAD mice. We suggest that obesity accelerates disease manifestation in a mouse model of AD via systemic immune exhaustion.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-36759-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36759-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-36759-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().