Differences in dexamethasone-sensitivity between lymphocytes from patients with Alzheimer's disease and patients with multi-infarct dementia.
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.
Nijhuis
E W
EW
Division of Immunological and Infectious Diseases, TNO Prevention and Health, Leiden, 2301 CE, The Netherlands.
Oostervink
F
F
Hinloopen
B
B
Rozing
J
J
Nagelkerken
L
L
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D015161:Dementia, Multi-Infarct / Q000276:immunology*; D003907:Dexamethasone / Q000494:pharmacology*; D004351:Drug Resistance; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D010835:Phytohemagglutinins; D019253:Proto-Oncogene Proteins c-bcl-2; D011965:Receptors, Glucocorticoid; C028697:dexamethasone receptor; D015847:Interleukin-4; D003907:Dexamethasone