Association of Subcortical Structural Shapes With Tau, Amyloid, and Cortical Atrophy in Early-Onset and Late-Onset Alzheimer’s Disease

The objectives of this study were to compare the topographical subcortical shape and to investigate the effects of tau or amyloid burden on atrophic patterns in early onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD). One hundred and sixty-one participants (53 EOAD, 44 LOAD, 33 young controls, and 31 older controls) underwent [18F]THK5351 positron emission tomography (PET), [18F]flutemetamol (FLUTE) PET, and 3T MRI scans. We used surface-based analysis to evaluate subcortical structural shape, permutation-based statistics for group comparisons, and Spearman’s correlations to determine associations with THK, FLUTE, cortical thickness, and neuropsychological test results. When compared to their age-matched controls, EOAD patients exhibited shape reduction in the bilateral amygdala, hippocampus, caudate, and putamen, while in LOAD patients, the bilateral amygdala and hippocampus showed decreased shapes. In EOAD, widespread subcortical shrinkage, with less association of the hippocampus, correlated with THK retention and cortical thinning, while in LOAD patients, subcortical structures were limited which had significant correlation with THK or mean cortical thickness. Subcortical structural shape showed less correlation with FLUTE global retention in both EOAD and LOAD. Multiple cognitive domains, except memory function, correlated with the bilateral amygdala, caudate, and putamen in EOAD patients, while more restricted regions in the subcortical structures were correlated with neuropsychological test results in LOAD patients. Subcortical structures were associated with AD hallmarks in EOAD. However, the correlation was limited in LOAD. Moreover, relationship between subcortical structural atrophy and cognitive decline were quite different between EOAD and LOAD. These findings suggest that the effects of Alzheimer’s pathologies on subcortical structural changes in EOAD and LOAD and they may have different courses of pathomechanism.