title: Clinical relevance of specific T-cell activation in the blood and cerebrospinal fluid of patients with mild Alzheimer's disease.
abstract: In Alzheimer's disease, the contribution of inflammation is still controversially discussed. The aim of this study was to identify a particular immune profile in the peripheral blood (PB) and cerebrospinal fluid (CSF) in patients with mild Alzheimer's disease (mAD) and mild cognitive impairment (MCI) and its potential functional relevance and association with neurodegeneration. A total of 88 patients with cognitive decline (54 mAD, 19 MCI, and 15 other dementias) were included in this study and compared with a group of younger (mean age, 31.3 years) and older (mean age, 68.9 years) healthy volunteers. Patients underwent detailed neurologic and neuropsychological examination, magnetic resonance imaging including voxel-based morphometry of gray matter, voxel-based diffusion tensor imaging, and white matter lesion volumetry, and PB and CSF analysis including multiparameter flow cytometry. Multiparameter flow cytometry revealed that proportions of activated HLA-DR positive CD4(+) and CD8(+) T-cells were slightly and significantly increased in the PB of MCI and mAD patients, respectively, when compared with healthy elderly controls but not in patients with other dementias. Although only a slight enhancement of the proportion of activated CD4(+) T-cells was observed in the CSF of both MCI and mAD patients, the proportion of activated CD8(+) T-cells was significantly increased in the CSF of mAD patients when compared with healthy elderly individuals. A slight increase in the proportion of activated CD8(+) T-cells was also observed in the intrathecal compartment of MCI patients. Activation of cytotoxic CD8(+) T-cells was considerably related to AD-typical neuropsychological deficits. Voxel-based regression analysis revealed a significant correlation between CD8(+) T-cell activation and microstructural tissue damage within parahippocampal areas as assessed by diffusion tensor imaging. Taken together, peripheral and intrathecal CD8(+) T-cell activation in mAD was significantly different from other dementias, suggesting a specific adaptive immune response. Lymphocyte activation seems to have a clinical impact because levels of activated CD8(+) T-cells were correlated with clinical and structural markers of AD pathology.
authors.affiliation: Department of Neurology, University Hospital Münster, Münster, Germany.
authors.forename: Gero
authors.initials: G
authors.lastname: Lueg
authors.affiliation: Department of Neurology, University Hospital Münster, Münster, Germany.
authors.forename: Catharina C
authors.initials: CC
authors.lastname: Gross
authors.affiliation: Department of Neurology, University Hospital Münster, Münster, Germany.
authors.forename: Hubertus
authors.initials: H
authors.lastname: Lohmann
authors.affiliation: Department of Neurology, University Hospital Münster, Münster, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Johnen
authors.affiliation: Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Kemmling
authors.affiliation: Department of Neurology, University Hospital Münster, Münster, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Deppe
authors.affiliation: Department of Neurology, University Hospital Münster, Münster, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Groger
authors.affiliation: Department of Neurology, University Hospital Münster, Münster, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Minnerup
authors.affiliation: Department of Neurology, University Hospital Münster, Münster, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.affiliation: Department of Neurology, University Hospital Münster, Münster, Germany.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.affiliation: Department of Neurology, University Hospital Münster, Münster, Germany. Electronic address: Thomas.Duning@ukmuenster.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Duning
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology / Q000523:psychology; D015415:Biomarkers; D001769:Blood / Q000276:immunology*; D001921:Brain / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002555:Cerebrospinal Fluid / Q000276:immunology*; D003071:Cognition; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology / Q000523:psychology; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests
chemical_list: D015415:Biomarkers
keywords: All cognitive disorders; Alzheimer's disease; CSF; Cerebrospinal fluid; Dementia; Neuroinflammation; PB; Peripheral blood; T-cells