Peripheral inflammatory biomarkers in Alzheimer's disease and mild cognitive impairment: a systematic review and meta‐analysis

Abstract

Background In the past few decades, it has been demonstrated with animal models and clinical studies that a chronic inflammatory process significantly contributes to Alzheimer's disease (AD) pathogenesis. Methods We systematically searched on PubMed and Web of Science for studies associated with peripheral inflammatory biomarkers in AD and mild cognitive impairment (MCI) before July 2018. Meta‐analysis was conducted to summarise results of studies relative to peripheral cytokines and chemokines in AD and MCI. Results Mean (± SD) concentrations of peripheral inflammatory biomarkers for AD, MCI and healthy controls were extracted from these studies. Our meta‐analysis revealed consistently elevated concentrations of inflammatory biomarkers such as C‐reactive protein, interleukin‐1β (IL‐1β), IL‐2, IL‐6, IL‐12, IL‐18, monocyte chemotactic protein‐1 (MCP‐1), MCP‐3, IL‐8 and interferon‐γ‐inducible protein 10 in AD patients, whereas no consistent results were obtained for elevated concentrations of cytokines or chemokines except MCP‐1 in MCI patients. Conclusions In conclusion, these results provided evidence to support that systematic inflammation might be a biomarker for AD diagnosis, whereas it might be a later event during AD disease progression.

A Path Toward Precision Medicine for Neuroinflammatory Mechanisms in Alzheimer's Disease

“…Modifications of the concentrations of several cytokines (160)(161)(162)(163)(164) and other inflammatory biomarkers associated with either microglia-e.g., soluble TREM2 (sTREM2), monocyte chemoattractant protein-1 (MCP-1), and YKL-40 (165-168)or astroglia, e.g., YKL-40 (161), are extensively investigated in AD patients. These alterations, potentially, reflect the inflammatory mechanisms within the CNS coupled with the neurodegenerative pathways (11,166).…”

“…The main issue concerning the peripheral measurements of inflammatory biomarkers is that they may not directly reflect brain neuroinflammation (163). Nonetheless, IL-6 and IL-1β concentrations are significantly higher in AD compared to cognitively normal controls in four meta-analysis (160)(161)(162)(163). IL-1β is a key molecule participating in the inflammatory response, cell proliferation, differentiation, and apoptosis.…”

“…In line with these findings, a longitudinal study reports the association of elevated plasma IL-6 levels with a greater risk of cognitive decay, at 2-year clinical follow-up. Other cytokines emerging as candidate peripheral inflammatory biomarkers are IL-2, IL-12, IL-18, and TGF-β (160)(161)(162)(163).…”

Is Innate Memory a Double-Edge Sword in Alzheimer's Disease? A Reappraisal of New Concepts and Old Data

“…In keeping with a potentiated trained immunity status of AD innate cells, several authors have reported elevated levels of circulating pro-inflammatory cytokines and amplified inflammatory response of blood cells in AD patients. Despite some inconsistent results, meta-analysis studies confirm an overall trend of increased pro-inflammatory cytokines in AD (82, 83), and higher levels of cytokines were observed in patients with early or mild forms of AD (84, 85). Similarly, peripheral innate cells of AD patients show a “primed” state and the percentage of peripheral monocytes producing pro-inflammatory cytokines increases early in AD (86).…”

Myeloproliferative blood cancers as a human neuroinflammation model for development of Alzheimer’s disease: evidences and perspectives

“…Interestingly, patients with AD exhibit elevated peripheral inflammatory cytokine levels very similar to those recorded in patients with MPNs, including elevated C-reactive protein, interleukin-1β (IL-1β), IL-2, IL-6,IL-8, IL-12, IL-18, soluble tumor necrosis factor receptor1 (sTNFR1), soluble tumor necrosis factor receptor2 (sTNFR2), monocyte chemotactic protein-1 (MCP-1), MCP-3, interferon-γ-inducible protein 10, and soluble CD40 ligand. Several of these inflammatory markers have also been found to be elevated in cerebrospinal fluid of patients with AD, including in addition elevated levels of IL-10, transforming growth factor-beta1 (TGFB1), YKL-40, and soluble triggering receptor expressed on myeloid cells2 (TREM2) [52,53].…”