Contributors: Amsterdam University Medical Centers (Amsterdam UMC); Universiteit Gent = Ghent University = Université de Gand (UGent); CIMC - Centre d'imagerie médicale de Cornavin; University of Medical Sciences / Beijing; Beijing Tongren Hospital; Sahlgrenska Academy at University of Gothenburg Göteborg; Göteborgs Universitet = University of Gothenburg (GU); Sahlgrenska University Hospital Gothenburg; University of Cambridge Cambridge, UK (CAM); Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS); Università degli Studi di Brescia = University of Brescia (UniBs); Hôpitaux Universitaires de Genève = University Hospital of Geneva Genève (HUG); Université de Genève = University of Geneva (UNIGE); Physiopathologie et imagerie des troubles neurologiques (PhIND); Université de Caen Normandie (UNICAEN); Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM); Institut Blood and Brain @ Caen-Normandie Caen (BB@C); CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie (CHU Caen Normandie); GIP Cyceron (Cyceron); Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie (CHU Caen Normandie); Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Toulouse NeuroImaging Center (ToNIC); Université Toulouse III - Paul Sabatier (UT3); Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI); Université Toulouse - Jean Jaurès (UT2J); Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Université Toulouse III - Paul Sabatier (UT3); Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Université Toulouse - Jean Jaurès (UT2J); Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Université Toulouse III - Paul Sabatier (UT3); Communauté d'universités et établissements de Toulouse (Comue de Toulouse); Service de Médecine Nucléaire - Rangueil CHU Toulouse; Pôle imagerie médicale CHU Toulouse; Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse); Center for Research and Advanced Therapies = Centro de Investigación y Terapias Avanzadas (CITA-Alzheimer); The University of Edinburgh; Imperial College London; Barcelonaβeta Brain Research Center (BBRC); Pasqual Maragall Foundation; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN); Instituto de Salud Carlos III Madrid (ISCIII)-ministerio de ciencia e innovacion; IMIM-Hospital del Mar; Generalitat de Catalunya = Generalidad de Cataluña = Government of Catalonia = Généralité de Catalogne; Alzheimer Center Amsterdam; VU University Medical Center Amsterdam; Maastricht University Maastricht; Karolinska Institutet = Karolinska Institute Stockholm; Vrije Universiteit Amsterdam Amsterdam (VU); University College London UCL (UCL); Universitat Pompeu Fabra Barcelona (UPF); EPAD is supported by the EU/EFPIA Innovative Medicines Initiative (IMI) grant agreement 115736. AM Wink, HM and FB are supported by AMYPAD (IMI115952).HM is supported by the Dutch Heart Foundation (2020T049), by the Eurostars-2 joint programme with cofunding from the European Union Horizon 2020 researchand innovation programme, provided by the Netherlands Enterprise Agency (RvO), and by the EU Joint Program for Neurodegenerative Disease Research, provided by the Netherlands Organisation for health Research and Development and Alzheimer Nederland. KB is supported by the Swedish Research Council (#2017-00915), the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB-201809-2016615), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986), the European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236), and the National Institute of Health (NIH), USA, (grant #1R01AG068398-01).JMW is supported by the UK Dementia Research Institute (Foundation Chair) which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. Dr. J.D. Gispert holds a ‘Ramón y Cajal’ fellowship (RYC2013-13054) from the Spanish Ministry of Economy andCompetitiveness, has received research support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking AMYPAD grant agreement n° 115952, and from Ministerio de Ciencia y Universidades (grant agreement RTI2018-102261).
نبذة مختصرة : International audience ; Gray matter networks are altered with amyloid accumulation in the earliest stage of AD, and are associated with decline throughout the AD spectrum. It remains unclear to what extent gray matter network abnormalities are associated with hyperphosphorylated-tau (p-tau). We studied the relationship of cerebrospinal fluid (CSF) p-tau181 with gray matter networks in non-demented participants from the European Prevention of Alzheimer's Dementia (EPAD) cohort, and studied dependencies on amyloid and cognitive status. Gray matter networks were extracted from baseline structural 3D T1w MRI. P-tau181 and abeta were measured with the Roche cobas Elecsys System. We studied the associations of CSF biomarkers levels with several network's graph properties. We further studied whether the relationships of p-tau 181 and network measures were dependent on amyloid status and cognitive stage (CDR). We repeated these analyses for network properties at a regional level, where we averaged local network values across cubes within each of 116 areas as defined by the automated anatomical labeling (AAL) atlas. Amyloid positivity was associated with higher network size and betweenness centrality, and lower gamma, clustering and small-world coefficients. Higher CSF p-tau 181 levels were related to lower betweenness centrality, path length and lambda coefficients (all p < 0.01). Three-way interactions between p-tau181, amyloid status and CDR were found for path length, lambda and clustering (all p < 0.05): Cognitively unimpaired amyloid-negative participants showed lower path length and lambda values with higher CSF p-tau181 levels. Amyloid-positive participants with impaired cognition demonstrated lower clustering coefficients in association to higher CSF p-tau181 levels. Our results suggest that alterations in gray matter network clustering coefficient is an early and specific event in AD.
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