%0 Journal Article
%A Heinzinger, Nils
%A Maass, Anne
%A Berron, David
%A Yakupov, Renat
%A Peters, Oliver
%A Fiebach, Jochen
%A Villringer, Kersten
%A Preis, Lukas
%A Priller, Josef
%A Spruth, Eike Jacob
%A Altenstein, Slawek
%A Schneider, Anja
%A Fliessbach, Klaus
%A Wiltfang, Jens
%A Bartels, Claudia
%A Jessen, Frank
%A Maier, Franziska
%A Glanz, Wenzel
%A Buerger, Katharina
%A Janowitz, Daniel
%A Perneczky, Robert
%A Rauchmann, Boris Stephan
%A Teipel, Stefan
%A Killimann, Ingo
%A Göerß, Doreen
%A Laske, Christoph
%A Munk, Matthias H
%A Spottke, Annika
%A Roy, Nina
%A Heneka, Michael T
%A Brosseron, Frederic
%A Dobisch, Laura
%A Ewers, Michael
%A Dechent, Peter
%A Haynes, John Dylan
%A Scheffler, Klaus
%A Wolfsgruber, Steffen
%A Kleineidam, Luca
%A Schmid, Matthias
%A Berger, Moritz
%A Düzel, Emrah
%A Ziegler, Gabriel
%T Exploring the ATN classification system using brain morphology.
%J Alzheimer's research & therapy
%V 15
%N 1
%@ 1758-9193
%C London
%I BioMed Central
%M DZNE-2023-00358
%P 50
%D 2023
%Z CC BY
%X The NIA-AA proposed amyloid-tau-neurodegeneration (ATN) as a classification system for AD biomarkers. The amyloid cascade hypothesis (ACH) implies a sequence across ATN groups that patients might undergo during transition from healthy towards AD: A-T-N-➔A+T-N-➔A+T+N-➔A+T+N+. Here we assess the evidence for monotonic brain volume decline for this particular (amyloid-conversion first, tau-conversion second, N-conversion last) and alternative progressions using voxel-based morphometry (VBM) in a large cross-sectional MRI cohort.We used baseline data of the DELCODE cohort of 437 subjects (127 controls, 168 SCD, 87 MCI, 55 AD patients) which underwent lumbar puncture, MRI scanning, and neuropsychological assessment. ATN classification was performed using CSF-Aβ42/Aβ40 (A+/-), CSF phospho-tau (T+/-), and adjusted hippocampal volume or CSF total-tau (N+/-). We compared voxel-wise model evidence for monotonic decline of gray matter volume across various sequences over ATN groups using the Bayesian Information Criterion (including also ROIs of Braak stages). First, face validity of the ACH transition sequence A-T-N-➔A+T-N-➔A+T+N-➔A+T+N+ was compared against biologically less plausible (permuted) sequences among AD continuum ATN groups. Second, we evaluated evidence for 6 monotonic brain volume progressions from A-T-N- towards A+T+N+ including also non-AD continuum ATN groups.The ACH-based progression A-T-N-➔A+T-N-➔A+T+N-➔A+T+N+ was consistent with cognitive decline and clinical diagnosis. Using hippocampal volume for operationalization of neurodegeneration (N), ACH was most evident in 9
%K Humans
%K Alzheimer Disease: diagnostic imaging
%K Cross-Sectional Studies
%K Bayes Theorem
%K Amyloid beta-Peptides
%K Cognitive Dysfunction: diagnostic imaging
%K Brain: diagnostic imaging
%K Amyloidogenic Proteins
%K tau Proteins
%K Biomarkers
%K Alzheimer’s disease (Other)
%K ATN (Other)
%K Alzheimer’s disease (Other)
%K Amyloid (Other)
%K Biomarker (Other)
%K MRI (Other)
%K Memory (Other)
%K VBM (Other)
%K Voxel-based morphometry (Other)
%K Amyloid beta-Peptides (NLM Chemicals)
%K Amyloidogenic Proteins (NLM Chemicals)
%K tau Proteins (NLM Chemicals)
%K Biomarkers (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:36915139
%2 pmc:PMC10009950
%R 10.1186/s13195-023-01185-x
%U https://pub.dzne.de/record/256606