TY  - JOUR
AU  - Biel, Davina
AU  - Steward, Anna
AU  - Dewenter, Anna
AU  - Dehsarvi, Amir
AU  - Zhu, Zeyu
AU  - Roemer-Cassiano, Sebastian N
AU  - Frontzkowski, Lukas
AU  - Hirsch, Fabian
AU  - Palleis, Carla
AU  - Höglinger, Günter
AU  - Brendel, Matthias
AU  - Franzmeier, Nicolai
TI  - A systematic comparison of ATN biomarkers for monitoring longitudinal cognitive changes in Alzheimer's disease
JO  - Alzheimer's and dementia
VL  - 21
IS  - 10
SN  - 1552-5260
CY  - Hoboken, NJ
PB  - Wiley
M1  - DZNE-2025-01188
SP  - e70783
PY  - 2025
AB  - INTRODUCTIONWith anti-amyloid beta (Aβ) therapies approved for Alzheimer's disease (AD), surrogate biomarkers are needed to monitor clinical treatment efficacy. Therefore, we systematically compared longitudinal changes in A/T/N biomarkers (amyloid-positron emission tomography [PET], tau-PET, plasma phosphorylated tau at threonine 217 [p-tau217], and magnetic resonance imaging) for tracking cognitive changes.METHODSWe analyzed longitudinal biomarker and cognitive change rates from the Alzheimer's Disease Neuroimaging Initiative (N = 141) and Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) (N = 151), estimated using linear mixed models. Using linear models, we tested biomarker changes as predictors of cognitive changes, comparing predictive strengths across biomarkers using bootstrapping.RESULTSTau-PET, plasma p-tau217, and cortical thickness changes accurately tracked change rates in Mini-Mental State Examination, Alzheimer's Disease Assessment Scale-Cognitive Subscale 13-item version, Clinical Dementia Rating-Sum of Boxes, and Preclinial Alzheimer Cognitive Composite scores. In contrast, amyloid-PET change rates were not linked to cognitive changes.DISCUSSIONPlasma p-tau217 offers a cost-effective AD-specific alternative to tau-PET and could potentially be implemented for monitoring cognitive changes in AD trials, while amyloid-PET lacks utility. Cortical thickness changes accurately track cognitive changes but may be confounded by pseudo-atrophy in anti-Aβ treatments.
LB  - PUB:(DE-HGF)16
DO  - DOI:10.1002/alz.70783
UR  - https://pub.dzne.de/record/281802
ER  -