Polymorphonuclear Neutrophil Functions are Differentially Altered in Amnestic Mild Cognitive Impairment and Mild Alzheimer’s Disease Patients

Article type: Research Article

Authors: Le Page, Aurélie^a | Lamoureux, Julie^b | Bourgade, Karine^a | Frost, Eric H.^c | Pawelec, Graham^{d; h} | Witkowski, Jacek M.^e | Larbi, Anis^f | Dupuis, Gilles^g | Fülöp, Tamàs^{a; *}

Affiliations: [a] Research Center on Aging, Graduate Program in Immunology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC, Canada | [b] Graduate Program in Physiology-Biophysics, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC, Canada | [c] Department of Microbiology and Infectiology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC, Canada | [d] Department of Internal Medicine II, Center for Medical Research University of Tübingen, Tübingen, Germany | [e] Department of Pathophysiology, Medical University of Gdańsk, Gdańsk, Poland | [f] Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A-Star), 8A Biomedical Grove, Immunos, Singapore | [g] Department of Biochemistry, Graduate Program in Immunology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC, Canada | [h] Health Sciences North Research Institute, Sudbury, ON, Canada

Correspondence: [*] Correspondence to: Tamàs Fülöp, MD, PhD, Research Center on Aging, Faculty of Medicine and Health Sciences, University of Sherbrooke, 3001, 12th Avenue North, Sherbrooke, Quebec, J1H 5N4, Canada. Tel.: +1 819 780 2220; Fax: +1 819 829 7141; E-mail: [email protected].

Abstract: The mechanisms of neurodegeneration in Alzheimer’s disease (AD) remain under investigation. Alterations in the blood-brain barrier facilitate exchange of inflammatory mediators and immune cells between the brain and the periphery in AD. Here, we report analysis of phenotype and functions of polymorphonuclear neutrophils (PMN) in peripheral blood from patients with amnestic mild cognitive impairment (aMCI, n = 13), patients with mild AD (mAD, n = 15), and healthy elderly controls (n = 13). Results showed an increased expression of CD177 in mAD but not in healthy or aMCI patients. IL-8 stimulated increased expression of the CD11b integrin in PMN of healthy subjects in vitro but PMN of aMCI and mAD patients failed to respond. CD14 and CD16 expression was lower in PMN of mAD but not in aMCI individuals relative to controls. Only PMN of aMCI subjects expressed lower levels of CD88. Phagocytosis toward opsonized E. coli was differentially impaired in PMN of aMCI and mAD subjects whereas the capacity to ingest Dextran particles was absent only in mAD subjects. Killing activity was severely impaired in aMCI and mAD subjects whereas free radical production was only impaired in mAD patients. Inflammatory cytokine (TNFα, IL-6, IL-1β, IL-12p70) and chemokine (MIP-1α, MIP-1β, IL-8) production in response to LPS stimulation was very low in aMCI and nearly absent in mAD subjects. TLR2 expression was low only in aMCI. Our data showed a differentially altered capacity of PMN of aMCI and mAD subjects to respond to pathological aggression that may impact impaired responses associated with AD development.

Keywords: Alzheimer’s disease, aMCI patients, polymorphonuclear neutrophils

DOI: 10.3233/JAD-170124

Journal: Journal of Alzheimer's Disease, vol. 60, no. 1, pp. 23-42, 2017