Peripheral inflammatory markers in Alzheimer’s disease: a systematic review and meta-analysis of 175 studies

TLDR: It is suggested that AD is accompanied by a peripheral inflammatory response and that IL-6 may be a useful biological marker to correlate with the severity of cognitive impairment and inversely correlated with mean MMSE scores.

Abstract: Objectives Increasing evidence suggests that inflammation is involved in Alzheimer’s disease (AD) pathology. This study quantitatively summarised the data on peripheral inflammatory markers in patients with AD compared with healthy controls (HC). Methods Original reports containing measurements of peripheral inflammatory markers in AD patients and HC were included for meta-analysis. Standardised mean differences were calculated using a random effects model. Meta-regression and exploration of heterogeneity was performed using publication year, age, gender, Mini-Mental State Examination (MMSE) scores, plasma versus serum measurements and immunoassay type. Results A total of 175 studies were combined to review 51 analytes in 13 344 AD and 12 912 HC patients. Elevated peripheral interleukin (IL)-1β, IL-2, IL-6, IL-18, interferon-γ, homocysteine, high-sensitivity C reactive protein, C-X-C motif chemokine-10, epidermal growth factor, vascular cell adhesion molecule-1, tumour necrosis factor (TNF)-α converting enzyme, soluble TNF receptors 1 and 2, α1-antichymotrypsin and decreased IL-1 receptor antagonist and leptin were found in patients with AD compared with HC. IL-6 levels were inversely correlated with mean MMSE scores. Conclusions These findings suggest that AD is accompanied by a peripheral inflammatory response and that IL-6 may be a useful biological marker to correlate with the severity of cognitive impairment. Further studies are needed to determine the clinical utility of these markers.