Abstract INTRODUCTION Brain atrophy patterns in Alzheimer's disease (AD) are well established, however, the contribution of alpha‐synuclein (α‐syn) copathology to these patterns remains unclear. This study investigates magnetic resonance imaging (MRI) ‐based atrophy patterns in AD patients with α‐syn copathology. METHODS We study two independent cohorts: Hospital Clinic Barcelona ( N = 139) and Alzheimer's Disease Neuroimaging Initiative (ADNI) ( N = 191). Participants were classified into AD–α‐syn seed amplification assay positive (αSAA+), AD‐αSAA‐, and healthy controls (CTR). Group comparisons of MRI regions were conducted using permutation tests adjusting for age and sex. RESULTS Compared to CTR, both AD‐αSAA‐ and AD‐αSAA+ showed widespread cortical thinning. Direct comparison of AD‐αSAA+ versus AD‐αSAA‐ revealed differential involvement of insular, entorhinal, lateral temporal, pre and postcentral gyrus, frontal cortices, and amygdala, although with minimum size effect. DISCUSSION α‐Syn copathology was associated with more extensive and pronounced atrophy, especially in frontal, lateral temporal, entorhinal, and amygdalar regions. This suggests that α‐syn is associated with greater neurodegeneration beyond typical AD patterns.
Esteller‐Gauxax et al. (Wed,) studied this question.