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Differences in dexamethasone-sensitivity between lymphocytes from patients with Alzheimer's disease and patients with multi-infarct dementia

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Author: Nijhuis, E.W.P. · Oostervink, F. · Hinloopen, B. · Rozing, J. · Nagelkerken, L.
Type:article
Date:1996
Institution: Gaubius Instituut TNO
Source:Brain, Behavior, and Immunity, 2, 10, 115-125
Identifier: 233352
doi: doi:10.1006/brbi.1996.0012
Keywords: Health · Glucocorticoid receptor · Clinical article · Cognitive defect · Drug sensitivity · Human cell · Lymphocyte · Mononuclear cell · Multiinfarct dementia · Screening · Aged · Aged, 80 and over · Alzheimer Disease · Apoptosis · Cells, Cultured · Dementia, Multi-Infarct · Dexamethasone · Drug Resistance · Female · Gene Expression Regulation · Humans · Immunosuppressive Agents · Interleukin-2 · Interleukin-4 · Lymphocyte Activation · Male · Phytohemagglutinins · Proto-Oncogene Proteins c-bcl-2 · Receptors, Glucocorticoid · T-Lymphocytes

Abstract

Peripheral blood mononuclear cells (PBMC) from 40 consecutive patients entering a screening program on cognitive impairment were studied in vitro with respect to their sensitivity to dexamethasone (DEX). Phytohemagglutinin-induced proliferation by PBMC from patients with senile dementia of the Alzheimer type (SDAT) was less sensitive to the inhibitory effect of DEX, compared to PBMC from patients with multi-infarct dementia (MID) and PBMC from patients with miscellaneous causes of cognitive impairment (MISC). An intermediate sensitivity was found with PBMC from patients with clinical signs of both MID and SDAT (= MIXED). These differences could not be explained by differences in the composition of the CD4+ T cell population, interleukin (IL)-2 or IL-4 production, or quantitative differences in the expression of glucocorticoid receptors as measured by flowcytometry. However, the expression of bcl-2 was higher in PBMC from SDAT patients than in cells from MID patients or from MISC patients, whereas the MIXED group showed an intermediate expression; a high bcl-2 expression correlated with a low DEX-sensitivity. These findings suggest that characteristics of PBMC reflect related changes in the central nervous system and indicate that PBMC may be a useful and accessible tool to obtain more insight into the pathogenesis of Alzheimer's disease. Chemicals/CAS: dexamethasone receptor; Dexamethasone, 50-02-2; Immunosuppressive Agents; Interleukin-2; Interleukin-4, 207137-56-2; Phytohemagglutinins; Proto-Oncogene Proteins c-bcl-2; Receptors, Glucocorticoid