NK Cells are Activated in Amnestic Mild Cognitive Impairment but not in Mild Alzheimer’s Disease Patients

Article type: Research Article

Authors: Le Page, Aurélie^a | Bourgade, Karine^a | Lamoureux, Julie^b | Frost, Eric^c | Pawelec, Graham^d | Larbi, Anis^e | Witkowski, Jacek M.^f | Dupuis, Gilles^g | Fülöp, Tamás^{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, 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] Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A-Star), 8A Biomedical Grove, Immunos, Singapore, Singapore | [f] Department of Pathophysiology, Medical University of Gdańsk, Gdańsk, Poland | [g] Department of Biochemistry, Graduate Program in Immunology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC, Canada

Correspondence: [*] Correspondence to: Tamás Fülöp, MD, PhD, Research Center on Aging, Faculty of Medicine and Health Sciences, University of Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC, J1H 5N4, Canada. Tel.: +1 819 780 2220; Fax: +1 819 829 7141; Tamas.Fulop@Usherbrooke.ca

Abstract: Alzheimerś disease (AD) is a progressive irreversible neurological brain disorder characterized by accumulation of amyloid-β, amyloid plaques, and neurofibrillary tangles. Inflammation and immune alterations have been linked to AD, suggesting that the peripheral immune system plays a role during the asymptomatic period of AD. NK cells participate in innate immune surveillance against intracellular pathogens and malignancy but their role in AD remains controversial. We have investigated changes in peripheral NK cell phenotypes and functions in amnestic mild cognitive impairment (aMCI, n = 10), patients with mild AD (mAD, n = 11), and healthy elderly controls (n = 10). Patients selected according to NINCDS-ADRDA criteria were classified using neuropsychological assessment tests. Phenotype analysis revealed differences in expression of CD16 (increased in mAD), NKG2A (decreased in aMCI), and TLR2 and TLR9 (both decreased in mAD). Functional assays revealed that NK cell killing activity and degranulation (CD107 expression) were unchanged in the three groups. In contrast, expression of the CD95 receptor was increased in aMCI and mAD. Granzyme B expression and cytokine production (TNFα, IFNγ) were increased in aMCI but not in mAD. CCL19- but not CCL21-dependent chemotaxis was decreased in aMCI and mAD, despite the fact that CCR7 expression was increased in aMCI. Our data suggest that the number of alterations observed in peripheral NK cells in aMCI represent an activation state compared to mAD patients and that may reflect an active immune response against a still to be defined aggression.

Keywords: Alzheimer’s disease, amnestic mild cognitive impairment, cell cytotoxicity, chemotaxis, natural killer cells, phenotyping, toll-like receptors

DOI: 10.3233/JAD-143054

Journal: Journal of Alzheimer's Disease, vol. 46, no. 1, pp. 93-107, 2015