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000256606 0247_ $$2pmid$$apmid:36915139
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000256606 037__ $$aDZNE-2023-00358
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000256606 1001_ $$0P:(DE-HGF)0$$aHeinzinger, Nils$$b0$$eFirst author
000256606 245__ $$aExploring the ATN classification system using brain morphology.
000256606 260__ $$aLondon$$bBioMed Central$$c2023
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000256606 520__ $$aThe 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.
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000256606 650_7 $$2Other$$aAlzheimer’s disease
000256606 650_7 $$2Other$$aATN
000256606 650_7 $$2Other$$aAlzheimer’s disease
000256606 650_7 $$2Other$$aAmyloid
000256606 650_7 $$2Other$$aBiomarker
000256606 650_7 $$2Other$$aMRI
000256606 650_7 $$2Other$$aMemory
000256606 650_7 $$2Other$$aVBM
000256606 650_7 $$2Other$$aVoxel-based morphometry
000256606 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000256606 650_7 $$2NLM Chemicals$$aAmyloidogenic Proteins
000256606 650_7 $$2NLM Chemicals$$atau Proteins
000256606 650_7 $$2NLM Chemicals$$aBiomarkers
000256606 650_2 $$2MeSH$$aHumans
000256606 650_2 $$2MeSH$$aAlzheimer Disease: diagnostic imaging
000256606 650_2 $$2MeSH$$aCross-Sectional Studies
000256606 650_2 $$2MeSH$$aBayes Theorem
000256606 650_2 $$2MeSH$$aAmyloid beta-Peptides
000256606 650_2 $$2MeSH$$aCognitive Dysfunction: diagnostic imaging
000256606 650_2 $$2MeSH$$aBrain: diagnostic imaging
000256606 650_2 $$2MeSH$$aAmyloidogenic Proteins
000256606 650_2 $$2MeSH$$atau Proteins
000256606 650_2 $$2MeSH$$aBiomarkers
000256606 693__ $$0EXP:(DE-2719)DELCODE-20140101$$5EXP:(DE-2719)DELCODE-20140101$$eLongitudinal Cognitive Impairment and Dementia Study$$x0
000256606 7001_ $$0P:(DE-2719)2811815$$aMaass, Anne$$b1$$udzne
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000256606 7001_ $$0P:(DE-2719)2811024$$aPeters, Oliver$$b4$$udzne
000256606 7001_ $$aFiebach, Jochen$$b5
000256606 7001_ $$aVillringer, Kersten$$b6
000256606 7001_ $$0P:(DE-2719)9000703$$aPreis, Lukas$$b7$$udzne
000256606 7001_ $$0P:(DE-2719)2811122$$aPriller, Josef$$b8$$udzne
000256606 7001_ $$0P:(DE-2719)2812446$$aSpruth, Eike Jacob$$b9$$udzne
000256606 7001_ $$0P:(DE-2719)2811720$$aAltenstein, Slawek$$b10$$udzne
000256606 7001_ $$0P:(DE-2719)2812035$$aSchneider, Anja$$b11$$udzne
000256606 7001_ $$0P:(DE-2719)2811326$$aFliessbach, Klaus$$b12$$udzne
000256606 7001_ $$0P:(DE-2719)2811317$$aWiltfang, Jens$$b13$$udzne
000256606 7001_ $$0P:(DE-2719)9000444$$aBartels, Claudia$$b14$$udzne
000256606 7001_ $$0P:(DE-2719)2000032$$aJessen, Frank$$b15$$udzne
000256606 7001_ $$aMaier, Franziska$$b16
000256606 7001_ $$0P:(DE-2719)2811614$$aGlanz, Wenzel$$b17$$udzne
000256606 7001_ $$0P:(DE-2719)2811351$$aBuerger, Katharina$$b18$$udzne
000256606 7001_ $$0P:(DE-2719)9002557$$aJanowitz, Daniel$$b19$$udzne
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000256606 7001_ $$aGöerß, Doreen$$b24
000256606 7001_ $$0P:(DE-2719)2000055$$aLaske, Christoph$$b25$$udzne
000256606 7001_ $$0P:(DE-2719)9001516$$aMunk, Matthias H$$b26$$udzne
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000256606 7001_ $$0P:(DE-2719)2812341$$aRoy, Nina$$b28$$udzne
000256606 7001_ $$0P:(DE-2719)2000008$$aHeneka, Michael T$$b29$$udzne
000256606 7001_ $$0P:(DE-2719)2810593$$aBrosseron, Frederic$$b30$$udzne
000256606 7001_ $$0P:(DE-2719)2811611$$aDobisch, Laura$$b31$$udzne
000256606 7001_ $$0P:(DE-2719)9000543$$aEwers, Michael$$b32$$udzne
000256606 7001_ $$aDechent, Peter$$b33
000256606 7001_ $$aHaynes, John Dylan$$b34
000256606 7001_ $$aScheffler, Klaus$$b35
000256606 7001_ $$0P:(DE-2719)2810544$$aWolfsgruber, Steffen$$b36$$udzne
000256606 7001_ $$0P:(DE-2719)2812139$$aKleineidam, Luca$$b37$$udzne
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000256606 7001_ $$aBerger, Moritz$$b39
000256606 7001_ $$0P:(DE-2719)2000005$$aDüzel, Emrah$$b40$$eLast author$$udzne
000256606 7001_ $$0P:(DE-2719)2814076$$aZiegler, Gabriel$$b41$$eLast author$$udzne
000256606 7001_ $$aInitiative, Alzheimer’s Disease Neuroimaging$$b42$$eCollaboration Author
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