Double Negative (IgG + IgD − CD27 − ) B Cells are Increased in a Cohort of Moderate-Severe Alzheimer's Disease Patients and Show a Pro-Inflammatory Trafficking Receptor Phenotype
Abstract
Alzheimer's disease (AD) is a progressive, irreversible, and debilitating disease for which no effective preventive or disease modifying therapies or treatments have so far been detected. The crucial step in AD pathogenesis is the production of amyloid-β 42 peptide, which causes chronic inflammation. Activated cells in the central nervous system (CNS) produce pro-inflammatory mediators that lead to the recruitment of myeloid or lymphocytic cells. As a consequence, the communication between the CNS and peripheral blood of AD subjects could influence the lymphocyte distribution and/or the expression of phenotypic markers. In the present paper, we show a significant decrease in total CD19 + B lymphocytes and a remodeling of the B cell subpopulations in moderate-severe AD patients, compared with their coeval healthy controls and mild AD subjects. In particular, we report a significant reduction in naïve B cells (IgD + CD27 − ) and a simultaneous increase in double negative (DN, IgD − CD27 − ) memory B lymphocytes. We have also evaluated the expression of the pro-inflammatory chemokine receptors CCR6 and CCR7 in total and naïve/memory B cells from mild and moderate-severe AD patients, with the aim to detect a possible relationship between the trafficking profile and the stage of the disease. Our results demonstrate that both the amount and the trafficking profile of B cells are related to the severity of AD. The results discussed in this paper suggest a well-selected antibody panel should be used as an additional test for the identification of early AD.
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In AD, increased circulating DN B cells display a pro-inflammatory trafficking receptor phenotype.
“In AD, increased circulating DN B cells display a proinflammatory trafficking receptor phenotype [78].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [78]
Pro-inflammatory chemokine receptors CCR6 and CCR7 were significantly upregulated on the surface of DN B cells in AD patients compared to healthy elderly controls.
“Accordingly, pro-inflammatory chemokine receptors CCR6 and CCR7 were significantly upregulated on the surface of DN B cells in AD pa tients compared to healthy elderly controls [78].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [78]
AD is associated with a significant and disease-specific disruption of B cell homeostasis.
“Altogether these data indicate that AD is associated with a significant and disease-specific disruption of B cell homeostasis.”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [78]
Previous findings showed a decrease in naïve IgD+ CD27 B cells in AD patients.
“These results confirm previous findings showing a decrease in naïve IgD + CD27 B cells in AD patients while refining the specific subpopulation of naïve B cells implicated”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [78]
B cell production and/or maturation are affected by AD.
“suggest that B cell production and/or maturation are affected by AD [78,93].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [78]
Analysis of the phenotype of circulating subpopulations of B cells in AD patients shows a decrease in naïve IgD+CD27- B cells and an increase in the percentage of double negative (DN) IgD-CD27- memory B cells.
“Analysis of the phenotype of circulating sub populations of B cells in AD patients shows a decrease in naïve IgD + CD27 B cells and an increase in the percentage of double negative (DN) IgD CD27 memory B cells [78].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [78]
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- Authors
- Bulati, M., Buffa, S., Martorana, A., Gervasi, F., Camarda, C., Azzarello, D. M., Monastero, R., Caruso, C., & Colonna-Romano, G.
- Affiliations
- University of Palermo (IT)
- Laboratory of experimental Oncohematology and cell cultures for clinical use, ARNAS CIVICO, Palermo, Italy
- Immunosenescence Unit, Department of Pathobiology and Medical and Forensic Biotechnologies (DIBIMEF), University of Palermo, Italy
- Venue
- Journal of Alzheimer’s Disease
- Publisher
- SAGE Publications
- Published
- 2015-02-19
- Volume
- 44
- Issue
- 4
- Pages
- 1241-1251
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1810076817
- Cited by
- 72
- References
- 65
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 11 · 2023: 7 · 2022: 7 · 2021: 8 · 2020: 7 · 2019: 5 · 2018: 4 · 2017: 6 · 2015: 2
- FWCI
- 2.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, B cell subsets
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Female, Flow Cytometry, Humans, Immunoglobulin D, Immunoglobulin G, Male, Mental Status Schedule, Phenotype, Cohort Studies, B-Lymphocyte Subsets, Tumor Necrosis Factor Receptor Superfamily, Member 7, Receptors, CCR6, Receptors, CCR7
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