BRAIN, BEHAVIOR, AND IMMUNITY 10, 115–125 (1996) ARTICLE NO. 0012 Differences in Dexamethasone-Sensitivity between Lymphocytes from Patients with Alzheimer’s Disease and Patients with Multi-Infarct Dementia ERIK W. P. NIJHUIS,FRITS OOSTERVINK,* BOUDEWIJN HINLOOPEN, JAN ROZING, AND LEX NAGELKERKEN Division of Immunological and Infectious Diseases, TNO Prevention and Health, P.O. Box 2215, 2301 CE Leiden, The Netherlands; and *General Psychiatric Hospital ‘‘Robert Fleury Foundation,’’ P.O. Box 422, 2260 AK, Leidschendam, The Netherlands Peripheral blood mononuclear cells (PBMC) from 40 consecutive patients entering a screen- ing 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 (Å 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.  1996 Academic Press, Inc. INTRODUCTION Various mechanisms are thought to play a role in the development of dementia. Whereas the vascular system plays a major role in the etiology of multi-infarct demen- tia (MID), senile dementia of the Alzheimer type (SDAT) is assumed to be related to alternative processing of amyloid precursor protein (APP) which in turn gives rise to the formation of b-amyloid (Hardy & Higgins, 1992), an important component of the so-called senile plaques (Glenner & Wong, 1984). Interestingly, parts of APP have been identified as natural inhibitors of the blood coagulation factors IXa and XIa, which also suggests an involvement of the vascular system in SDAT (Smith, Higuchi, & Broze, 1990; Schmaier, Dahl, Rozemuller, Roos, Wagner, Chung, & Van Nostrand, 1993). Another neuropathological hallmark of SDAT is the presence of neurofibrillary tangles (Kidd, 1963). At present, a definitive diagnosis of SDAT can only be established postmortem since no biological markers are available, although progress is being made in this respect (Farlow, Ghetti, Benson, Farrow, Van Nostrand, & Wagner, 1992; Van Nos- trand, Wagner, Shankle, Farrow, Dick, Rozemuller, Kuiper, Wolters, Zimmerman, Cotman, & Cunningham, 1992). Such biological markers are of value in order to discriminate between MID and SDAT. Furthermore, such markers would be of impor- tance to gain more insight into the etiology and pathogenesis of these diseases. Recent observations support the idea that characteristics of peripheral blood mono- 115 0889-1591/96 $18.00 Copyright  1996 by Academic Press, Inc. All rights of reproduction in any form reserved.