TY  - JOUR
AU  - Heinzinger, Nils
AU  - Maass, Anne
AU  - Berron, David
AU  - Yakupov, Renat
AU  - Peters, Oliver
AU  - Fiebach, Jochen
AU  - Villringer, Kersten
AU  - Preis, Lukas
AU  - Priller, Josef
AU  - Spruth, Eike Jacob
AU  - Altenstein, Slawek
AU  - Schneider, Anja
AU  - Fliessbach, Klaus
AU  - Wiltfang, Jens
AU  - Bartels, Claudia
AU  - Jessen, Frank
AU  - Maier, Franziska
AU  - Glanz, Wenzel
AU  - Buerger, Katharina
AU  - Janowitz, Daniel
AU  - Perneczky, Robert
AU  - Rauchmann, Boris Stephan
AU  - Teipel, Stefan
AU  - Killimann, Ingo
AU  - Göerß, Doreen
AU  - Laske, Christoph
AU  - Munk, Matthias H
AU  - Spottke, Annika
AU  - Roy, Nina
AU  - Heneka, Michael T
AU  - Brosseron, Frederic
AU  - Dobisch, Laura
AU  - Ewers, Michael
AU  - Dechent, Peter
AU  - Haynes, John Dylan
AU  - Scheffler, Klaus
AU  - Wolfsgruber, Steffen
AU  - Kleineidam, Luca
AU  - Schmid, Matthias
AU  - Berger, Moritz
AU  - Düzel, Emrah
AU  - Ziegler, Gabriel
TI  - Exploring the ATN classification system using brain morphology.
JO  - Alzheimer's research & therapy
VL  - 15
IS  - 1
SN  - 1758-9193
CY  - London
PB  - BioMed Central
M1  - DZNE-2023-00358
SP  - 50
PY  - 2023
N1  - CC BY
AB  - 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
KW  - Humans
KW  - Alzheimer Disease: diagnostic imaging
KW  - Cross-Sectional Studies
KW  - Bayes Theorem
KW  - Amyloid beta-Peptides
KW  - Cognitive Dysfunction: diagnostic imaging
KW  - Brain: diagnostic imaging
KW  - Amyloidogenic Proteins
KW  - tau Proteins
KW  - Biomarkers
KW  - Alzheimer’s disease (Other)
KW  - ATN (Other)
KW  - Alzheimer’s disease (Other)
KW  - Amyloid (Other)
KW  - Biomarker (Other)
KW  - MRI (Other)
KW  - Memory (Other)
KW  - VBM (Other)
KW  - Voxel-based morphometry (Other)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Amyloidogenic Proteins (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
KW  - Biomarkers (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:36915139
C2  - pmc:PMC10009950
DO  - DOI:10.1186/s13195-023-01185-x
UR  - https://pub.dzne.de/record/256606
ER  -