title: NK Cells are Activated in Amnestic Mild Cognitive Impairment but not in Mild Alzheimer's Disease Patients.
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.
authors.affiliation: Research Center on Aging, Graduate Program in Immunology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Le Page
authors.affiliation: Research Center on Aging, Graduate Program in Immunology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Karine
authors.initials: K
authors.lastname: Bourgade
authors.affiliation: Graduate Program in Physiology-Biophysics, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Lamoureux
authors.affiliation: Department of Microbiology and Infectiology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Frost
authors.affiliation: Department of Internal Medicine II, Center for Medical Research University of Tübingen, Tübingen, Germany.
authors.forename: Graham
authors.initials: G
authors.lastname: Pawelec
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A-Star), 8A Biomedical Grove, Immunos, Singapore, Singapore.
authors.forename: Anis
authors.initials: A
authors.lastname: Larbi
authors.affiliation: Department of Pathophysiology, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Jacek M
authors.initials: JM
authors.lastname: Witkowski
authors.affiliation: Department of Biochemistry, Graduate Program in Immunology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Gilles
authors.initials: G
authors.lastname: Dupuis
authors.affiliation: Research Center on Aging, Graduate Program in Immunology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Tamás
authors.initials: T
authors.lastname: Fülöp
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D000704:Analysis of Variance; D053327:Apolipoprotein E4 / Q000235:genetics; D060825:Cognitive Dysfunction / Q000235:genetics / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology; D020014:K562 Cells / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009483:Neuropsychological Tests; D018121:Receptors, Cytokine / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D053327:Apolipoprotein E4; D016207:Cytokines; D018121:Receptors, Cytokine; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D018664:Interleukin-12
keywords: Alzheimer’s disease; amnestic mild cognitive impairment; cell cytotoxicity; chemotaxis; natural killer cells; phenotyping; toll-like receptors