Altered expression of costimulatory molecules in dementias

Abstract

Although the expression of co-stimulatory molecules plays an important role in the immune system, only little is known about their regulation in dementias. Therefore, we determined the expression of CD28, ICOS (CD278) and CTLA-4 (CD152) by CD4 + and CD8 + T cells in the peripheral blood of patients with mild cognitive impairment (MCI; N = 19), Alzheimer's disease (AD; N = 51), vascular dementia (VD; N = 21) and frontotemporal dementia (FTD; N = 6) at the point in time of diagnosis compared to 19 non-demented elderly persons. The expression of CD28 and ICOS by CD4 + and CD8 + T cells was not changed in AD, FTD or VD patients. The expression of the negative regulator CTLA-4 was increased by CD4 + T cells from AD and FTD patients and by CD8 + T cells from VD patients. The classification of the AD patients according to the severity of the disorder showed stage-dependent alterations of CD28, ICOS and CTLA-4 expression. In AD patients, the correlation analysis showed an association between the decline in CD28 + T cells and the increase in CTLA-4 + T cells with cognitive decline, measured by the mini-mental state examination (MMSE), tau proteins and Amyloid-β, important AD biomarkers in cerebrospinal fluid (CSF). In FTD patients, a positive association between Q Albumin, a marker for blood-CSF-barrier function, and CD28 and a negative correlation between Q Albumin and ICOS expression were determined. Our data suggest a dysregulated balance between the expression of negative and positive co-stimulatory molecules by T cells in AD patients, which might contribute to chronic inflammation observed in dementia.

Keywords: Alzheimer’s disease; Costimulation; Frontotemporal dementia; T cells; Vascular dementia.

Fig. 1

Expression of CTLA-4 in AD, VD and FTD. The expression of the negative regulator CTLA-4 on CD4 + T cells (a) and CD8 + T cells (b) from non-demented controls and patients with AD, VD and FTD at diagnosis were shown as percentage. *p < 0.05

Fig. 2

Expression of CTLA-4 in MCI and in stages of AD. The expression of CD28 (a), ICOS (b) and CTLA-4 (c) on CD4 + T lymphocytes were determined in patients suffering from MCI and AD patients grouped according to the severity of symptoms in mild, moderate and severe and compared to non-demented volunteers. *p < 0.05