Reduced frequency of T lymphocytes expressing CTLA-4 in frontotemporal dementia compared to Alzheimer's disease

Abstract

Studies suggest that inflammation is involved in the neurodegenerative cascade of dementias. Immunological mechanisms may be part of the pathophysiological process in frontotemporal dementia (FTD), but up till now only vague evidence of such mechanisms has been presented. The B7- CD28/CTLA-4 pathway is an important immunological signaling pathway involved in modulation of T cell activation. The aim of this study was to compare the expression of molecules associated with co-stimulatory signaling in peripheral blood mononuclear cells (PBMC) of FTD to Alzheimer disease (AD) and control groups. Our results confirm the previous demonstrated increased expression of CD80 in CD14+ Alzheimer patients T cells but show, for the first time, a reduction in the expression of CTLA-4 in CD4+ FTD cells. As CTLA-4 is the most potent negative regulators of T-cell activation we speculated that peripheral T lymphocytes in FTD are more activated and this could be involved in the neurodegeneration observed in this dementia.

Keywords: AD; APC; Alzheimer; Alzheimer Disease; B7-1; B7-2; CD80; CD86; CNS; CTLA-4; CTRL; FTD; Frontotemporal dementia; HLA-DR; MHC; MMSE; Mine-mental state examination; PBMC; PNAF; SD; T lymphocytes; T-cell-receptor; TCR; antigen presenting cell; behavioural-variant frontotemporal dementia; bvFTD; central nervous system; control patients; cytotoxic T-lymphocyte antigen-4 or CD152; human leukocyte antigen complex; major-histocompatibility-complex; peripheral blood mononuclear cells; progressive nonfluent aphasia; semantic dementia.