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Research paper
Peripheral inflammatory markers in Alzheimer’s disease: a systematic review and meta-analysis of 175 studies
  1. Ka Sing P Lai1,2,
  2. Celina S Liu1,3,
  3. Allison Rau1,3,
  4. Krista L Lanctôt1,3,4,
  5. Cristiano A Köhler5,
  6. Maureen Pakosh6,
  7. André F Carvalho5,
  8. Nathan Herrmann1,3,4
  1. 1 Neuropsychopharmacology Research Group, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  2. 2 Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
  3. 3 Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada
  4. 4 Departments of Psychiatry, University of Toronto, Toronto, Ontario, Canada
  5. 5 Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
  6. 6 Toronto Rehabilitation Institute, University Health Network, Toronto, Ontario, Canada
  1. Correspondence to Dr Nathan Herrmann, Neuropsychopharmacology Research Group, Sunnybrook Health Sciences Center, 2075 Bayview Avenue, Suite FG08, Toronto, Ontario M4N 3M5, Canada; nathan.herrmann{at}


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.

  • cytokines
  • chemokines
  • adipokines
  • inflammation
  • alzheimer’s disease

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  • Contributors KSPL, CSL and AR were involved in the planning, data extraction, data analysis, and writing of the manuscript. MP was involved in data acquisition for the manuscript. CAK and AFC were involved in editing the manuscript. KLL and NH were involved in planning, editing and overseeing completeness of the manuscript.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.