Cortical asymmetry in autosomal dominant Alzheimer’s disease progression - Research findings

Sep 30, 2026

Uploaded by Ben

Cortical asymmetry index was used to characterize brain hemispheric thickness asymmetry across the Alzheimer’s disease continuum. Baseline T1-weighted MRI from 60 Clinic Barcelona mutation carriers and independent longitudinal data from 564 participants in the Dominantly Inherited Alzheimer Network observational study were analyzed, with cerebrospinal fluid and plasma neurofilament light included when available. Freesurfer-based thickness and open-source asymmetry calculations supported cross-sectional group comparisons by clinical status and APOE ε4. Longitudinal generalized additive models evaluated symptom-proximal progression. Higher asymmetry distinguished asymptomatic and symptomatic carriers from controls and tracked with elevated neurofilament light, lower mini-mental state examination, and nearer onset proximity, with symptomatic carriers showing longitudinal increases.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Cortical asymmetry index and study aim

Imaging and biomarker pipeline

Cohorts and participants

Cross-sectional analyses

Longitudinal modeling

Key findings and implications

[https://doi.org/10.1093/braincomms/fcaf488](https://doi.org/10.1093/braincomms/fcaf488) BRAIN COMMUNICATIONS 2026: fcaf488 | 1 BRAIN COMMUNICATIONS Cortical asymmetry in autosomal dominant Alzheimer’s disease progression Agnès Pérez-Millan, 1,2,3 Neus Falgàs, 1,3 Beatriz Bosch, 1,3 Sergi Borrego-Écija, 1,3 Anna Antonell, 1,3 Guadalupe Fernández-Villullas, 1,3 Diana Esteller-Gauxax, 1,4 Adrià Tort-Merino, 1,3 Núria Bargalló,5,6 Mircea Balasa, 1,3 Albert Lladó, 1,3,4 David Aguillon,7 Patricio Chrem,8 Gregory S. Day,9 Emma Devenney, 10 Edward D. Huey, 11 Takeshi Ikeuchi, 12 Mathias Jucker, 13, 14 Kensaku Kasuga, 15 Jonathan Vöglein, 16, 17 Jee Hoon Roh, 18 Paolo Vitali, 19 Ana Luisa Sosa Ortiz,20 Jorge J. Llibre-Guerra,21 Brian A. Gordon,21 Eric McDade,21 Randall J. Bateman21 and Raquel Sánchez-Valle 1,3,4, The Dominantly Inherited Alzheimer Network (DIAN) 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. Received June 24, 2025. Revised November 04, 2025. Accepted December 17, 2025. Advance access publication December 19, 2025 © The Author(s) 2025. Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed und

FAQs

What does the cortical asymmetry index measure in this study?

It evaluates cortical thickness asymmetry between hemispheres to quantify brain structural differences across the Alzheimer’s disease continuum.

Which cohorts were used for the analyses?

Clinic Barcelona provided 60 baseline T1-weighted MRI scans, and the Dominantly Inherited Alzheimer Network observational study contributed independent baseline and longitudinal MRI data from 564 participants.

How was cortical asymmetry linked to clinical progression and biomarkers?

Higher cortical asymmetry in mutation carriers correlated with higher plasma (and when available cerebrospinal fluid) neurofilament light, lower mini-mental state examination, and closer proximity to symptom onset; asymmetry also increased over time in symptomatic mutation carriers.

Sep 30, 2026

Uploaded by Ben