Multivariate analysis of differential lymphocyte cell cycle activity in Alzheimer's disease

Abstract

Mounting evidence suggests cell cycle dysregulation is involved in the pathogenesis of Alzheimer's disease (AD) and that this failure is systemic, affecting not only neurons but also peripheral blood lymphocytes (PBLs). This study analyzed if differences in PBL proliferation activity could be used as a diagnostic biomarker for AD. CD69 and CD28 expressions on PBL T, B, and monocyte cells were measured by flow cytometry with and without mitogenic stimulation in healthy controls (HC), probable AD, and Parkinson's disease dementia (PDD) subjects. Univariate and multivariate scoring models were employed to evaluate the data relative to the clinical diagnoses. Eleven CD expression markers were significantly altered in AD subjects compared with a mixed pool of PDD and HC subjects using univariate models. Using multivariate models, seven CD expression markers were significantly altered in AD subjects compared with PDD subjects. Multivariate scoring demonstrated up to a 91% positive and 92% negative agreement with subject clinical diagnosis and had little correlation with the severity of dementia. Present findings suggest that with further development this analytical and multivariate modeling procedure could aid the current differential diagnosis of Alzheimer's disease.

Search for Alzheimer's Disease Biomarkers in Blood Cells: Hypotheses-Driven Approach

“…Using univariate models in AD subjects eleven CD expression markers were found to be significantly changed compared with a mixed pool of HC and PD subjects [59]. The results suggest future science group www.futuremedicine.com…”

“…Using univariate models in AD subjects eleven CD expression markers were found to be significantly changed compared with a mixed pool of HC and PD subjects [59]. The results suggest future science group www.futuremedicine.com that both for the pathomechanism of AD and the development of AD diagnostic markers, a systemic failure of cellular proliferation control is critically important.…”

Progranulin deficiency induces overactivation of WNT5A expression via TNF-α/NF-κB pathway in peripheral cells from frontotemporal dementia-linked granulin mutation carriers

“…46,[52][53][54] For this reason, peripheral cells, such as fibroblasts or blood lymphocytes, have been used extensively in the search for useful biomarkers that may correlate with expression and/or progression of disease. [55][56][57][58] In this regard, it has been shown that peripheral cells from patients with neurodegenerative disorders display cell cycle disturbances, 45,[59][60][61][62] reflecting the unscheduled cell cycle re-entry of postmitotic neurons and leading to apoptotic cell death. [63][64][65] The present work was undertaken to elucidate possible mechanisms involved in the PGRN deficiencyinduced WNT5A expression and signalling in PGRNdeficient lymphoblasts from patients with FTLD-TDP that were considered responsible for the increased activation of the CDK6/pRb-mediated cell proliferation.…”

Differential processing of amyloid precursor protein in brain and in peripheral blood leukocytes

“…Sultana et al, 2011; Stieler et al, 2012), we did not distinguish among subclasses. However, we argue our data are not the product of any small subclass of leukocytes because the vast majority of cells were immunopositive (Fig.…”