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.
Highlights
Alzheimer disease (AD) is the most common neurodegenerative disorder worldwide
Semi-Quantitative Analysis of 120 Proteins Through Protein-Arrays Approach Forty-nine patients of clinically characterized diagnosis were included for the protein-array analysis: the cohort was composed of individuals with pre-symptomatic (MCI, mild cognitive impairment, n = 20) or late-stage AD (n = 14) patients and from control subjects (n = 15), Figure 1A
The possibility to identify a blood-based panel of biomarkers to detect AD patients could allow for a systematic and early diagnosis of them, at the time of the first signs indicative of cognitive impairment, optimizing their care and treatment
Summary
Alzheimer disease (AD) is the most common neurodegenerative disorder worldwide. It is characterized by progressive memory loss and cognitive function deficit. Inflammation is present from pre-clinical to terminal stages of the disease, as reflected by activated microglia and reactive astrocytes that surround plaques. Microglia activation is a complex phenomenon, resulting in various phenotypes of the cells (secreting different types of cytokines), indicative of their interaction with the environment and allowing for either inflammatory or antiinflammatory responses. The reactive astrocytes that accumulate around the plaques participate in the clearance of Aβ deposits and in cytokine secretion, enhancing the neuroinflammatory response initiated by microglia [for review, see Ref. The reactive astrocytes that accumulate around the plaques participate in the clearance of Aβ deposits and in cytokine secretion, enhancing the neuroinflammatory response initiated by microglia [for review, see Ref. [3]]
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