TY  - JOUR
AU  - Pérez-Millan, Agnès
AU  - Falgàs, Neus
AU  - Bosch, Beatriz
AU  - Borrego-Écija, Sergi
AU  - Antonell, Anna
AU  - Fernández-Villullas, Guadalupe
AU  - Esteller-Gauxax, Diana
AU  - Tort-Merino, Adrià
AU  - Bargalló, Núria
AU  - Balasa, Mircea
AU  - Lladó, Albert
AU  - Aguillon, David
AU  - Chrem, Patricio
AU  - Day, Gregory S
AU  - Devenney, Emma
AU  - Huey, Edward D
AU  - Ikeuchi, Takeshi
AU  - Jucker, Mathias
AU  - Kasuga, Kensaku
AU  - Vöglein, Jonathan
AU  - Roh, Jee Hoon
AU  - Vitali, Paolo
AU  - Sosa Ortiz, Ana Luisa
AU  - Llibre-Guerra, Jorge J
AU  - Gordon, Brian A
AU  - McDade, Eric
AU  - Bateman, Randall J
AU  - Sánchez-Valle, Raquel
TI  - Cortical asymmetry in autosomal dominant Alzheimer's disease progression.
JO  - Brain communications
VL  - 8
IS  - 1
SN  - 2632-1297
CY  - [Oxford]
PB  - Oxford University Press
M1  - DZNE-2026-00062
SP  - fcaf488
PY  - 2026
AB  - The cortical asymmetry index evaluates the cortical thickness asymmetry between hemispheres. We investigated cortical asymmetry index in asymptomatic and symptomatic mutation carriers of autosomal dominant Alzheimer's disease to explore the brain asymmetry within the Alzheimer's disease continuum. Sixty baseline T1-weighted MRI scans were obtained from the Clinic Barcelona cohort. Baseline and longitudinal MRI data from 564 participants within the dominantly inherited Alzheimer network observational study were used as an independent, confirmatory cohort. Cerebrospinal fluid and plasma neurofilament light chain levels were included when available. Cortical thickness was calculated using Freesurfer and cortical asymmetry index was calculated via an open-source pipeline. Cross-sectional analyses examined cortical asymmetry index differences based on clinical classification and APOE ε4 status, adjusting for age, sex and estimated years from onset, while correlations were assessed with age, estimated years from onset, mini-mental state examination scores, and neurofilament light. Longitudinal cortical asymmetry index evolution was modelled using generalized additive models in the dominantly inherited Alzheimer network observational study cohort, incorporating age, sex, and the interaction between group and estimated years from onset. The cortical asymmetry index successfully distinguished asymptomatic mutation carrier and symptomatic mutation carriers from healthy controls in the Clinic Barcelona cohort and symptomatic mutation carriers from controls in dominantly inherited Alzheimer network observational study. Higher cortical asymmetry index in mutation carriers (asymptomatic mutation carrier and symptomatic mutation carriers combined) and in symptomatic mutation carriers were associated with higher plasma neurofilament light levels, a closer proximity to symptom onset, and lower mini-mental state examination in the Clinic Barcelona cohort. In the dominantly inherited Alzheimer network observational study cohort, mutation carriers exhibited increased cortical asymmetry index compared to controls and correlated with elevated neurofilament light (plasma and Cerebrospinal fluid), lower mini-mental state examination, and a closer proximity to symptom onset. APOE3/3 carriers showed greater asymmetry than other APOE genotypes and significant cortical asymmetry index differences between asymptomatic mutation carrier and symptomatic mutation carriers. Longitudinally, cortical asymmetry index increased over time significantly in symptomatic mutation carriers. These findings underscore brain asymmetry as a potential biomarker for early Alzheimer's disease progression in autosomal dominant Alzheimer's disease, with implications for detection and monitoring tracking disease-related neuroanatomical changes.
KW  - APOE (Other)
KW  - Alzheimer’s disease (Other)
KW  - autosomal dominant Alzheimer’s disease (Other)
KW  - brain (Other)
KW  - magnetic resonance imaging (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41523185
C2  - pmc:PMC12781868
DO  - DOI:10.1093/braincomms/fcaf488
UR  - https://pub.dzne.de/record/283183
ER  -