% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Heinzinger:256606,
author = {Heinzinger, Nils and Maass, Anne and Berron, David and
Yakupov, Renat and Peters, Oliver and Fiebach, Jochen and
Villringer, Kersten and Preis, Lukas and Priller, Josef and
Spruth, Eike Jacob and Altenstein, Slawek and Schneider,
Anja and Fliessbach, Klaus and Wiltfang, Jens and Bartels,
Claudia and Jessen, Frank and Maier, Franziska and Glanz,
Wenzel and Buerger, Katharina and Janowitz, Daniel and
Perneczky, Robert and Rauchmann, Boris Stephan and Teipel,
Stefan and Killimann, Ingo and Göerß, Doreen and Laske,
Christoph and Munk, Matthias H and Spottke, Annika and Roy,
Nina and Heneka, Michael T and Brosseron, Frederic and
Dobisch, Laura and Ewers, Michael and Dechent, Peter and
Haynes, John Dylan and Scheffler, Klaus and Wolfsgruber,
Steffen and Kleineidam, Luca and Schmid, Matthias and
Berger, Moritz and Düzel, Emrah and Ziegler, Gabriel},
collaboration = {Initiative, Alzheimer’s Disease Neuroimaging},
title = {{E}xploring the {ATN} classification system using brain
morphology.},
journal = {Alzheimer's research $\&$ therapy},
volume = {15},
number = {1},
issn = {1758-9193},
address = {London},
publisher = {BioMed Central},
reportid = {DZNE-2023-00358},
pages = {50},
year = {2023},
note = {CC BY},
abstract = {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 $9\%$ of gray
matter predominantly in the medial temporal lobe. Many
cortical regions suggested alternative non-monotonic volume
progressions over ACH progression groups, which is
compatible with an early amyloid-related tissue expansion or
sampling effects, e.g., due to brain reserve. Volume decline
in $65\%$ of gray matter was consistent with a progression
where A status converts before T or N status (i.e., ACH/ANT)
when compared to alternative sequences (TAN/TNA/NAT/NTA).
Brain regions earlier affected by tau tangle deposition
(Braak stage I-IV, MTL, limbic system) present stronger
evidence for volume decline than late Braak stage ROIs
(V/VI, cortical regions). Similar findings were observed
when using CSF total-tau for N instead.Using the ATN
classification system, early amyloid status conversion
(before tau and neurodegeneration) is associated with brain
volume loss observed during AD progression. The ATN system
and the ACH are compatible with monotonic progression of MTL
atrophy.DRKS00007966, 04/05/2015, retrospectively
registered.},
subtyp = {Review Article},
keywords = {Humans / Alzheimer Disease: diagnostic imaging /
Cross-Sectional Studies / Bayes Theorem / Amyloid
beta-Peptides / Cognitive Dysfunction: diagnostic imaging /
Brain: diagnostic imaging / Amyloidogenic Proteins / tau
Proteins / Biomarkers / Alzheimer’s disease (Other) / ATN
(Other) / Alzheimer’s disease (Other) / Amyloid (Other) /
Biomarker (Other) / MRI (Other) / Memory (Other) / VBM
(Other) / Voxel-based morphometry (Other) / Amyloid
beta-Peptides (NLM Chemicals) / Amyloidogenic Proteins (NLM
Chemicals) / tau Proteins (NLM Chemicals) / Biomarkers (NLM
Chemicals)},
cin = {AG Düzel / AG Maaß / AG Berron / AG Dirnagl / AG Priller
/ AG Endres / AG Schneider / Patient Studies Bonn / AG
Wiltfang / AG Jessen / AG Dichgans / AG Gasser / Clinical
Research Platform (CRP) / AG Teipel / Biomarker / AG Simons
/ AG Wagner / AG Schmid Bonn},
ddc = {610},
cid = {I:(DE-2719)5000006 / I:(DE-2719)1311001 /
I:(DE-2719)5000070 / I:(DE-2719)1810002 / I:(DE-2719)5000007
/ I:(DE-2719)1811005 / I:(DE-2719)1011305 /
I:(DE-2719)1011101 / I:(DE-2719)1410006 / I:(DE-2719)1011102
/ I:(DE-2719)5000022 / I:(DE-2719)1210000 /
I:(DE-2719)1011401 / I:(DE-2719)1510100 / I:(DE-2719)1011301
/ I:(DE-2719)1110008 / I:(DE-2719)1011201 /
I:(DE-2719)1013028},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 351 -
Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-351},
experiment = {EXP:(DE-2719)DELCODE-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36915139},
pmc = {pmc:PMC10009950},
doi = {10.1186/s13195-023-01185-x},
url = {https://pub.dzne.de/record/256606},
}