Systemic Immune Responses in Alzheimer's Disease: In Vitro Mononuclear Cell Activation and Cytokine Production
Open accessAbstract
To investigate the systemic signs of immune-inflammatory responses in Alzheimer's disease (AD), in the present study we have analyzed blood lymphocyte subsets and the expression of activation markers on peripheral blood mononuclear cells (PBMCs) from AD patients and age-matched healthy controls (HC) activated in vitro by recombinant amyloid-beta peptide (rAbeta42). Our study of AD lymphocyte subpopulations confirms the already described decrease of the absolute number and percentage of B cells when compared to HC lymphocytes, whereas the other subsets are not significantly different in patients and controls. We report the increased expression of the activation marker CD69 and of the chemokine receptors CCR2 and CCR5 on T cells but no changes of CD25 after activation. B cells are also activated by rAbeta42 as demonstrated by the enhanced expression of CCR5. Moreover, rAbeta42 induces an increased expression of the scavenger receptor CD36 on monocytes. Some activation markers and chemokine receptors are overexpressed in unstimulated AD cells when compared to controls. This is evidence of the pro-inflammatory status of AD. Stimulation by rAbeta42 also induces the production of the pro-inflammatory cytokines IL-1beta, IL-6, IFN-gamma, and TNF-alpha, and of the anti-inflammatory cytokines IL-10 and IL-1Ra. The chemokines RANTES, MIP-1beta, and eotaxin as well as some growth factors (GM-CSF, G-CSF) are also overproduced by AD-derived PBMC activated by rAbeta42. These results support the involvement of systemic immunity in AD patients. However, our study is an observational one so we cannot draw a conclusion about its contribution to the pathophysiology of the disease.
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The diminishing B cells in AD is more pronounced in females.
“our findings revealed that the diminishing B cells in AD is more pronounced in females”
From Distinct sex-specific DNA methylation differences in Alzheimer’s disease (2022) · cites this paper as [70]
The Lymphocyte subsets section reports fewer circulating B cells in AD patients than in healthy controls, but not a larger decrease in females. The PBMC activation section states that the results were not affected by gender, contrary to the claimed female difference. Page numbers are unavailable in our copy. (LLM, conf=0.86)
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References 43 · Cited by 86
Research works printed but not linked: 3
- Di Bona D, Candore G, Franceschi C, Licastro F, Colonna- Romano G, Cammà C, Lio D, Caruso C (2009) Systematic review by meta-analyses on the possible role of TNF-alpha polymorphisms in association with Alzheimer's disease. Brain Res Rev 61, 60-68.
- Di Bona D, Plaia A, Vasto S, Cavallone L, Lescai F, Franceschi C, Licastro F, Colonna-Romano G, Lio D, Candore G, Caru- so C (2008) Association between the interleukin-1beta poly- morphisms and Alzheimer's disease: a systematic review and meta-analysis. Brain Res Rev 59, 155-163.
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- Authors
- Pellicanò, M., Bulati, M., Buffa, S., Barbagallo, M., Di Prima, A., Misiano, G., Picone, P., Di Carlo, M., Nuzzo, D., Candore, G., Vasto, S., Lio, D., Caruso, C., & Colonna-Romano, G.
- Affiliations
- University of Palermo (IT)
- Dipartimento di Medicina Clinica e delle Patologie Emergenti, Università di Palermo, Italy
- Istituto di Biomedicina e di Immunologia Molecolare Alberto Monroy (IT)
- Istituto di Biomedicina e Immunologia Molecolare, CNR, Palermo, Italy
- Gruppo di Studio sull'Immunosenescenza, Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Italy
- Corresponding author
- Caruso, Calogero
- ORCID
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2010-07-08
- Volume
- 21
- Issue
- 1
- Pages
- 181-192
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1499647695
- Cited by
- 86
- References
- 43
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 6 · 2023: 3 · 2022: 10 · 2021: 3 · 2020: 5 · 2019: 2 · 2018: 6 · 2017: 8 · 2016: 1 · 2015: 14 · 2014: 6 · 2013: 9 · 2012: 7
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion, other-oa)
- Funders
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Università degli Studi di Palermo
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, systemic immunity
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Analysis of Variance, Cells, Cultured, Female, Flow Cytometry, Gene Expression Regulation, Humans, Leukocytes, Mononuclear, Lymphocytes, Male, Middle Aged, Peptide Fragments, Time Factors, Case-Control Studies, Cytokines, Amyloid beta-Peptides
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