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Sex Differences in Innate Immune Response of Peripheral Blood Leukocytes of Alzheimer’s Disease Patients

Abstract

Neurodegenerative disorders, including Alzheimer’s disease (AD), are associated with a disruption of normal immune function that could potentially impact the brain. In AD sex and gender have been noted as relevant to disease prevalence or clinical manifestation. It is suggested that disease progression could vary as a result of the different inflammation state among males and females. The objective was to investigate sex-dependent difference in innate immunity of AD patients and healthy, age-matched controls. The level of innate immunity was measured with test based on peripheral blood leukocytes (PBLs) resistance to viral infection (vesicular stomatitis virus, VSV) ex vivo. Cytokine: TNF-α, IFN-γ, IL-1β, IL-10 production by uninfected and VSV-infected PBLs ex vivo with enzyme-linked immunosorbent assay were examined. In contrast to controls, women with AD exhibit lower average level of innate immunity than AD men. The mean level of TNF-α, IL-10 and IL-1β was higher in AD men than in AD women whereas such changes were not observed among controls. The level of IFN-γ was higher in AD than in controls. PBLs from AD did not increase IFN-γ production after viral infection in contrast to controls. Leukocytes from women with AD exhibited a weaker response to viral infection and much less cytokine production compared to men with AD. It is important to consider sex as a biological variable in AD as it shows promises to advance our understanding of mechanisms of AD pathology and may be the basis for future treatment of AD.

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Data Availability

Data available on request from the authors.

Abbreviations

B12:

Vitamin B12/cobalamin

BBB:

Blood–brain barrier

CNS:

Central nervous system

CRP:

C-reactive protein

CT:

Computed tomography

DGN:

The diagnostic according to the guidelines of the German Society of Neurology

DSMV:

Fifth edition of diagnostic and statistical manual of mental disorders classification (criteria for major neurocognitive disorder)

FBS:

Fetal bovine serum

GSK3:

Glycogen synthase kinase 3

IFN:

Interferon

IL:

Interleukin

MMSE:

Mini-mental state examination

MRI:

Magnetic resonance imaging

NINCDS-ADRDA:

National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer’s Disease and Related Disorders Association

PBLs:

Peripheral blood leukocytes

PMA:

Phorbol 12-myristate 13-acetate

TCID50 :

Fifty-percent tissue culture infective dose

TNF:

Tumor necrosis factor

TSH:

Thyroid-stimulating hormone

VSV:

Vesicular stomatitis virus

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Acknowledgements

The authors wish to acknowledge the nursing staff of the Wroclaw Medical University for the support in recruiting participants and blood samples collection.

Funding

This work was supported by internal research funds of the Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences and Wroclaw Medical University.

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Authors and Affiliations

Authors

Contributions

JL, MS: contributed to the study conception and design. MO, MS: performed laboratory experiments. JL: was responsible for clinical examination of the patients. Data collection and analysis were performed by MS, MO and MS. The first draft of the manuscript was written by MS and MS. MS, JL, BO revised the manuscript critically for important intellectual content and editing language. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Marta Sochocka.

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Conflict of Interest

The authors report no conflicts of interest, financial or otherwise.

Ethical Approval

This study has been reviewed, approved, and conducted in accordance with the guidelines of the Ethics Committee of the Wroclaw Medical University (No. KB-349/2016).

Consent to Participate

Informed consent was obtained from all individual participants or their legal guardians included in the study.

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Not applicable.

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Sochocka, M., Ochnik, M., Sobczyński, M. et al. Sex Differences in Innate Immune Response of Peripheral Blood Leukocytes of Alzheimer’s Disease Patients. Arch. Immunol. Ther. Exp. 70, 16 (2022). https://doi.org/10.1007/s00005-022-00653-w

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  • DOI: https://doi.org/10.1007/s00005-022-00653-w

Keywords

  • Alzheimer’s disease
  • Innate immunity
  • PBLs
  • Cytokine production
  • Inflammation