Frederic Brosseron1,2, Carl-Christian Kolbe3, Francesco Santarelli1,2, Stephanie Carvalho4, Anna Antonell5, Sergio Castro-Gomez1, Pawel Tacik1, Aishwarya Alex Namasivayam6, Graziella Mangone4, Reinhard Schneider6, Eicke Latz2,3, Ullrich Wüllner2,7, Per Svenningsson8, Raquel Sánchez-Valle5, José Luis Molinuevo9, Jean-Christophe Corvol4, Michael T Heneka1,2. 1. Department of Neurodegenerative Diseases & Geropsychiatry/Neurology, University of Bonn Medical Center, Bonn, Germany. 2. German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. 3. University of Bonn Medical Center, Institute of Innate Immune, Bonn, Germany. 4. Institut du Cerveau et de la Moelle épinière, Sorbonne Université, Assistance-Publique Hôpitaux de Paris, INSERM, UMRS 1127, CNRS, UMR 7225, Institut du Cerveau et de la Moelle épinière, ICM, Hôpital Pitié-Salpêtrière, Department of Neurology, Centre d'Investigation Clinique Neurosciences, Paris, France. 5. Alzheimer's disease and other cognitive disorders Unit, Hospital Clínic, Fundació Clínic per a la Recerca Biomèdica, Institut d'Investigacions Biomè; diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. 6. Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Campus Belval, Belvaux, Luxembourg. 7. Department of Neurology, University of Bonn Medical Center, Bonn, Germany. 8. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. 9. Barcelonabeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain.
Abstract
INTRODUCTION: Multiple immunity biomarkers have been suggested as tracers of neuroinflammation in neurodegeneration. This study aimed to verify findings in cerebrospinal fluid (CSF) samples of Alzheimer's disease (AD) and Parkinson's disease (PD) subjects from the network of the European, Innovative Medicines Initiative-funded project AETIONOMY. METHODS: A total of 227 samples from the studies/centres AETIONOMY, ICEBERG, and IDIBAPS were used to analyse 21 selected immunity biomarkers in CSF. Results were compared to data of an independent cohort of 399 subjects previously published. RESULTS: Immunity markers were predominantly and reproducibly associated with pathological levels of tau isoforms, but also with amyloid levels, aging, sex, APOE genotype, and center-specific factors. DISCUSSION: Immunity biomarker levels in CSF reflect molecular and cellular pathology rather than diagnosis in neurodegenerative disorders. Assay standardization and stratification for age and other covariates could improve the power of such markers in clinical applications or intervention studies targeting immune responses in neurodegeneration.
INTRODUCTION: Multiple immunity biomarkers have been suggested as tracers of neuroinflammation in neurodegeneration. This study aimed to verify findings in cerebrospinal fluid (CSF) samples of Alzheimer's disease (AD) and Parkinson's disease (PD) subjects from the network of the European, Innovative Medicines Initiative-funded project AETIONOMY. METHODS: A total of 227 samples from the studies/centres AETIONOMY, ICEBERG, and IDIBAPS were used to analyse 21 selected immunity biomarkers in CSF. Results were compared to data of an independent cohort of 399 subjects previously published. RESULTS: Immunity markers were predominantly and reproducibly associated with pathological levels of tau isoforms, but also with amyloid levels, aging, sex, APOE genotype, and center-specific factors. DISCUSSION: Immunity biomarker levels in CSF reflect molecular and cellular pathology rather than diagnosis in neurodegenerative disorders. Assay standardization and stratification for age and other covariates could improve the power of such markers in clinical applications or intervention studies targeting immune responses in neurodegeneration.
Authors: Sofia Bergström; Julia Remnestål; Jamil Yousef; Jennie Olofsson; Ioanna Markaki; Stephanie Carvalho; Jean-Christophe Corvol; Kim Kultima; Lena Kilander; Malin Löwenmark; Martin Ingelsson; Kaj Blennow; Henrik Zetterberg; Bengt Nellgård; Frederic Brosseron; Michael T Heneka; Beatriz Bosch; Raquel Sanchez-Valle; Anna Månberg; Per Svenningsson; Peter Nilsson Journal: Ann Clin Transl Neurol Date: 2021-06-15 Impact factor: 4.511
Authors: Hyun-Sik Yang; Can Zhang; Becky C Carlyle; Sherri Y Zhen; Bianca A Trombetta; Aaron P Schultz; Jeremy J Pruzin; Colleen D Fitzpatrick; Wai-Ying W Yau; Dylan R Kirn; Dorene M Rentz; Steven E Arnold; Keith A Johnson; Reisa A Sperling; Jasmeer P Chhatwal; Rudolph E Tanzi Journal: Alzheimers Dement Date: 2021-06-23 Impact factor: 16.655