Camilla Steen Jensen1, Justyna Maria Bahl2, Lærke Borg Østergaard3, Peter Høgh4, Lene Wermuth5, Amanda Heslegrave6, Henrik Zetterberg7, Niels H H Heegaard8, Steen Gregers Hasselbalch9, Anja Hviid Simonsen10. 1. Danish Dementia Research Centre, Department of Neurology, Rigshospitalet University of Copenhagen, DK-2100 Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Denmark. Electronic address: Camilla.steen.jensen@regionh.dk. 2. Department of Bioanalysis, Lundbeck, 2500 Valby, Denmark. 3. Danish Dementia Research Centre, Department of Neurology, Rigshospitalet University of Copenhagen, DK-2100 Copenhagen, Denmark. Electronic address: Lærke.borg.østergaard@regionh.dk. 4. Department of Clinical Medicine, University of Copenhagen, Denmark; Regional Dementia Research Centre, Department of Neurology, Zealand University Hospital, DK-4000 Roskilde, Denmark. Electronic address: phh@regionsjaelland.dk. 5. Dementia Clinic, Department of Neurology, Odense University Hospital, DK-5000 Odense, Denmark. Electronic address: Lene.Wermuth@rsyd.dk. 6. Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, WC1N London, UK; UK Dementia Research Institute at UCL, London WC1E 6BT, UK. Electronic address: a.heslegrave@ucl.ac.uk. 7. Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, WC1N London, UK; UK Dementia Research Institute at UCL, London WC1E 6BT, UK; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, S-431 80 Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, S-431 80 Mölndal, Sweden. Electronic address: henrik.zetterberg@clinchem.gu.se. 8. Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark; Department of Clinical Biochemistry, University of Southern Denmark, Odense, Denmark. 9. Danish Dementia Research Centre, Department of Neurology, Rigshospitalet University of Copenhagen, DK-2100 Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Denmark. Electronic address: Steen.gregers.hasselbalch@regionh.dk. 10. Danish Dementia Research Centre, Department of Neurology, Rigshospitalet University of Copenhagen, DK-2100 Copenhagen, Denmark. Electronic address: anja.hviid.simonsen@regionh.dk.
Abstract
BACKGROUND: Neuroinflammation is recognized as part of the pathological progression of Alzheimer's disease (AD), but the molecular mechanisms are still not entirely clear. Systemically, physical exercise has shown to have a positive modulating effect on markers of inflammation. It is not known if this general effect also takes place in the central nervous system in AD. The aim of this study was to investigate the effect of 16 weeks of moderate to high-intensity physical exercise on selected biomarkers of inflammation both systemically and in the CNS, in patients with AD. METHODS:Plasma and cerebrospinal fluid (CSF) from 198 patients with Alzheimer's disease participating in the Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: The Effect of Physical Exercise (ADEX) study were analyzed for concentrations of 8‑isoprostane, soluble trigger receptor expressed on myeloid cells 2 (sTREM2), and the MSD v-plex proinflammation panel 1 human containing interferon gamma (IFNγ), Interleukin-10 (IL10), IL12p70, IL13, IL1β, IL2, IL4, IL6, IL8, and tumor necrosis factor alpha (TNFα), before and after a 16-week intervention with physical exercise, and we studied whether changes were modulated by the patients' APOE genotype. RESULTS: Most inflammatory markers remained unchanged after exercise. We found an increasing effect of 16 weeks of physical exercise on sTREM2 measured in CSF. Further, IL6 in plasma increased in the exercise group after physical exercise (mean relative change 41.03, SD 76.7), compared to controls (-0.97, SD 49.4). In a sub-analysis according to APOE genotype, we found that in ε4 carriers, exercise had a stabilizing effect on IFNγ concentration with a mean relative change of 7.84 (SD 42.6), as compared to controls (114.7 (SD 188.3), p = 0.038. CONCLUSION: Our findings indicate an effect of physical exercise on markers of neuroinflammation in CSF measured by an increase in sTREM2 in patients with AD. Further, there may be a small inflammatory systemic effect related to physical exercise in patients with AD.
RCT Entities:
BACKGROUND: Neuroinflammation is recognized as part of the pathological progression of Alzheimer's disease (AD), but the molecular mechanisms are still not entirely clear. Systemically, physical exercise has shown to have a positive modulating effect on markers of inflammation. It is not known if this general effect also takes place in the central nervous system in AD. The aim of this study was to investigate the effect of 16 weeks of moderate to high-intensity physical exercise on selected biomarkers of inflammation both systemically and in the CNS, in patients with AD. METHODS: Plasma and cerebrospinal fluid (CSF) from 198 patients with Alzheimer's disease participating in the Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: The Effect of Physical Exercise (ADEX) study were analyzed for concentrations of 8‑isoprostane, soluble trigger receptor expressed on myeloid cells 2 (sTREM2), and the MSD v-plex proinflammation panel 1 human containing interferon gamma (IFNγ), Interleukin-10 (IL10), IL12p70, IL13, IL1β, IL2, IL4, IL6, IL8, and tumor necrosis factor alpha (TNFα), before and after a 16-week intervention with physical exercise, and we studied whether changes were modulated by the patients' APOE genotype. RESULTS: Most inflammatory markers remained unchanged after exercise. We found an increasing effect of 16 weeks of physical exercise on sTREM2 measured in CSF. Further, IL6 in plasma increased in the exercise group after physical exercise (mean relative change 41.03, SD 76.7), compared to controls (-0.97, SD 49.4). In a sub-analysis according to APOE genotype, we found that in ε4 carriers, exercise had a stabilizing effect on IFNγ concentration with a mean relative change of 7.84 (SD 42.6), as compared to controls (114.7 (SD 188.3), p = 0.038. CONCLUSION: Our findings indicate an effect of physical exercise on markers of neuroinflammation in CSF measured by an increase in sTREM2 in patients with AD. Further, there may be a small inflammatory systemic effect related to physical exercise in patients with AD.
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