Proinflammatory and anti-inflammatory cytokines in the CSF of patients with Alzheimer's disease and their correlation with cognitive decline

• Published in: Neurobiology of aging 2019-04, Vol.76, p.125-132
• Main Authors: Taipa, Ricardo, das Neves, Sofia P., Sousa, Ana L., Fernandes, Joana, Pinto, Claudia, Correia, Ana P., Santos, Ernestina, Pinto, Pedro S., Carneiro, Paula, Costa, Patricio, Santos, Diana, Alonso, Isabel, Palha, Joana, Marques, Fernanda, Cavaco, Sara, Sousa, Nuno
• Format: Article
• Language: English
• Subjects: Aged; Alzheimer Disease - diagnosis; Alzheimer Disease - immunology; Alzheimer Disease - psychology; Alzheimer's disease; Biomarkers - cerebrospinal fluid; Cerebrospinal fluid; Ciências Médicas; Cognition; Cognitive Dysfunction - diagnosis; Cognitive Dysfunction - immunology; Cognitive Dysfunction - psychology; Cytokines; Cytokines - cerebrospinal fluid; Disease Progression; Female; Humans; Inflammation; Inflammation Mediators - cerebrospinal fluid; Male; Medicina Básica; Middle Aged; Neuroinflammation; Prospective Studies; Science & Technology; Up-Regulation
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2018.12.019

Cumulative data suggest that neuroinflammation plays a prominent role in Alzheimer's disease (AD) pathogenesis. The purpose of this work was to assess if patients with AD present a specific cerebrospinal fluid (CSF) cytokine profile and if it correlates to disease progression. We determined the levels of 27 cytokines in CSF of patients with AD and compared them with patients with frontotemporal dementia and nondemented controls. In addition, we correlated the cytokine levels with cognitive status and disease progression after 12 months. Patients with AD had higher levels of proinflammatory and anti-inflammatory cytokines (eotaxin, interleukin [IL]-1ra, IL-4, IL-7, IL-8, IL-9, IL-10, IL-15, granulocyte colony-stimulating factor, monocyte chemotactic protein 1, platelet-derived growth factor, tumor necrosis factor alfa) compared to nondemented controls. There was a negative correlation between the disease progression and the levels of several cytokines (IL-1β, IL-4, IL-6, IL-9, IL-17A, basic fibroblast growth factor, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon gamma, macrophage inflammatory proteins-1β). To the best of our knowledge, this is the first study reporting a “protective” role of the upregulation of specific intrathecal cytokine levels in AD. This finding supports that a fine “rebalancing” of the immune system represents a new target in AD therapeutic approach. •AD patients have high levels of pro- and anti-inflammatory cytokines in the CSF.•CSF inflammatory changes are less prominent in patients with frontotemporal dementia.•Pro- and anti-inflammatory cytokines correlated positively with cognition in AD patients.•Cytokine levels correlated negatively with disease progression in AD patients.