Exploratory study on immune phenotypes in Alzheimer’s Disease and vascular dementia

BACKGROUND: The differentiation of Alzheimer's disease (AD) dementia from vascular dementia (VaD), and mixed-type dementia requires stepwise analysis and usually occurs late in the disease process. Early diagnosis and therapy monitoring would benefit greatly from the identification of biomarkers of neurodegeneration, especially blood biomarkers. To this end, the aim of this pilot study was to investigate differences in the distribution of peripheral T-cell populations in patients with AD compared to VaD and mixed dementia. METHODS: Flow cytometry was performed on blood samples from 11 AD, 6 VaD, 6 mixed dementia patients, and 17 healthy controls (HC). CD4+ and CD8+ T-cells were typed for expression of CD45, CD27, CD28, CD25, FoxP3, CCR4 and CCR6; the other leukocytes were also assessed. Functionally, immune cell uptake of the β-Amyloid (Aβ1-42 ) toxic fragment was also evaluated. RESULTS: A higher proportion of CD4+CD28- memory T-cells and a reciprocal reduction of CD4+CD28+CD27+ naive T-lymphocytes was detected in all patient groups relative to controls. Significantly fewer CD4+CD25+FoxP3 regulatory T-cells were present in VaD, and significantly more CCR6+ and CCR4+ CD4+ T-cells in AD. Higher CCR6+ T-cells frequencies were also present in mixed dementia patients, potentially due to the inflammation and immune cell chemoattraction triggered by Aβ. CONCLUSIONS: This study is a comprehensive investigation comparing different kinds of dementia, revealing differentially-expressed peripheral markers, potentially useful for early AD, VaD and mixed dementia diagnosis, that would assist in proper treatments for these disparate diseases. Validation is now required.