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, 44 (4), 1241-51

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

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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

Matteo Bulati et al. J Alzheimers Dis.

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-β42 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.

Keywords: Aging; Alzheimer's disease; B cells; CCR6; CCR7; trafficking profile.

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