Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Aug:184:106202.
doi: 10.1016/j.nbd.2023.106202. Epub 2023 Jun 15.

Sex-based differences in effector cells of the adaptive immune system during Alzheimer's disease and related dementias

Jenny Lutshumba  1 , Donna M Wilcock  2 , Nancy L Monson  3 , Ann M Stowe  4
Affiliations
Review

Sex-based differences in effector cells of the adaptive immune system during Alzheimer's disease and related dementias

Jenny Lutshumba et al. Neurobiol Dis. 2023 Aug.

Abstract

Neurological conditions such as Alzheimer's disease (AD) and related dementias (ADRD) present with many challenges due to the heterogeneity of the related disease(s), making it difficult to develop effective treatments. Additionally, the progression of ADRD-related pathologies presents differently between men and women. With two-thirds of the population affected with ADRD being women, ADRD has presented itself with a bias toward the female population. However, studies of ADRD generally do not incorporate sex-based differences in investigating the development and progression of the disease, which is detrimental to understanding and treating dementia. Additionally, recent implications for the adaptive immune system in the development of ADRD bring in new factors to be considered as part of the disease, including sex-based differences in immune response(s) during ADRD development. Here, we review the sex-based differences of pathological hallmarks of ADRD presentation and progression, sex-based differences in the adaptive immune system and how it changes with ADRD, and the importance of precision medicine in the development of a more targeted and personalized treatment for this devastating and prevalent neurodegenerative condition.

Keywords: B lymphcoytes; Dementia; Estrogen; T lymphocytes; Tesosterone.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Summary of the effects of Alzheimer’s disease and related dementia and sex hormones on the brain. ADRD effects on Brain structure, genetic factors and Alzheimer’s disease biomarkers, and Sex hormones effects on the brain in men and women. Symbols: ↑increase, ↓decrease,♀women, ♂ men. Abbreviations: ADRD: Alzheimer’s disease and related dementia, SNP: single nucleotide polymorphisms, WMH: White matter hyperintensity, Aβ: Amyloid Beta, BBB: Blood-brain barrier.
Fig. 2.
Fig. 2.
Effect of sex hormones and age on circulating effector immune cells and difference in Alzheimer’s disease biomarker between men and women. Abbreviations: AD: Alzheimer’s disease. Th: Helper T cells, Treg: Regulatory T cells, NKT: Natural Killer T cells, γδ: gamma delta, Aβ: Amyloid beta. Symbols: ↑increase, ↓decrease, ♀ women, ♂ men.
See this image and copyright information in PMC

References

    1. Abbas AK, Murphy KM, Sher A, 1996. Functional diversity of helper T lymphocytes. Nature 383 (6603), 787–793. - PubMed
    1. Abdullah M, et al., 2012. Gender effect on in vitro lymphocyte subset levels of healthy individuals. Cell. Immunol 272 (2), 214–219. - PubMed
    1. Afshan G, Afzal N, Qureshi S, 2012. CD4+CD25(hi) regulatory T cells in healthy males and females mediate gender difference in the prevalence of autoimmune diseases. Clin. Lab 58 (5–6), 567–571. - PubMed
    1. Ahlbom E, Prins GS, Ceccatelli S, 2001. Testosterone protects cerebellar granule cells from oxidative stress-induced cell death through a receptor mediated mechanism. Brain Res. 892 (2), 255–262. - PubMed
    1. Aliseychik M, et al., 2020. Dissection of the human T-cell receptor gamma gene repertoire in the brain and peripheral blood identifies age- and Alzheimer’s disease-associated clonotype profiles. Front. Immunol 11, 12. - PMC - PubMed

Publication types