ABSTRACT
Brain inflammation is one of the hallmarks of Alzheimer disease (AD) and a current trend is that inflammatory mediators, particularly cytokines and chemokines, may represent valuable biomarkers for early screening and diagnosis of the disease. Various studies have reported differences in serum level of cytokines, chemokines, and growth factors in patients with mild cognitive impairment or AD. However, data were often inconsistent and the exact function of inflammation in neurodegeneration is still a matter of debate. In the present work, we measured the expression of 120 biomarkers (corresponding to cytokines, chemokines, growth factors, and related signaling proteins) in the serum of 49 patients with the following diagnosis distribution: 15 controls, 14 AD, and 20 MCI. In addition, we performed the same analysis in the cerebrospinal fluid (CSF) of 20 of these patients (10 AD and 10 controls). Among the biomarkers tested, none showed significant changes in the serum, but 13 were significantly modified in the CSF of AD patients. Interestingly, all of these biomarkers were implicated in neurogenesis or neural stem cells migration and differentiation. In the second part of the study, 10 of these putative biomarkers (plus 4 additional) were quantified using quantitative multiplex ELISA methods in the CSF and the serum of an enlarged cohort composed of 31 AD and 24 control patients. Our results confirm the potential diagnosis interest of previously published blood biomarkers, and proposes new ones (such as IL-8 and TNFR-I). Further studies will be needed to validate these biomarkers which could be used alone, combined, or in association with the classical amyloid and tau biomarkers.
ABSTRACT
To improve the etiological diagnosis of neurodegenerative dementias like Alzheimer's disease (AD) or frontotemporal dementia (FTD), we evaluated the value of individual and combined measurements of the following relevant cerebrospinal fluid (CSF) biomarkers: Tau, 181p-Tau, Aß38, Aß40, Aß42, sAßPPα, and sAßPPß. This study conducted in two centers included patients with FTD (n = 34), AD (n = 52), as well as a control group of persons without dementia (CTRL, n = 42). Identical clinical criteria and pre-analytical conditions were used while CSF biomarkers were measured using commercial single and multiplex quantitative immunoassays. Thorough statistical analyses, including ROC curves, logistic regressions, and decision trees, were performed. We validated in AD the specific increase of p-Tau levels and the decrease of Aß42 levels, two biological hallmarks of this disease. Tau concentrations were highest in AD and intermediate in FTD when compared to CTRL. The most interesting results were obtained by focusing on amyloid biomarkers as we found out in FTD a significant decrease of sAßPPß, Aß38, and Aß40 levels. Aß38 in particular was the most useful biomarker to differentiate FTD subjects from the CTRL population. Combining p-Tau and Aß38 led us to correctly classifying FTD patients with sensitivity at 85% and specificity at 82%. Significant changes in amyloid biomarkers, particularly for Aß38, are therefore seen in FTD. This could be quite useful for diagnosis purposes and it might provide additional evidence on the interrelationship between Tau and AßPP biology which understanding is essential to progress towards optimal therapeutic and diagnostic approaches of dementia.