Yvon Galis-de Graaf, Netherlands
Amsterdam UMC, location VUmc Anatomy and NeurosciencesAuthor Of 1 Presentation
CORTICAL THICKNESS IN ALZHEIMER’S DISEASE: DIFFERENTIAL CONTRIBUTIONS OF AMYLOID-BETA AND P-TAU LOAD
Abstract
Aims
Alzheimer’s disease (AD) is characterized by cortical atrophy on MRI and abnormal depositions of amyloid-beta, p-tau and inflammation pathologically. However, the relative contribution of these pathological hallmarks to cortical atrophy, widely used as MRI biomarker in AD, is yet to be defined. The aim of this study is to determine the independent and combined contributions of the pathological hallmarks to cortical thickness in AD descents.
Methods
Twenty pathologically confirmed AD donors and ten age-matched controls underwent post-mortem in-situ 3T 3DT1 MRI, from which cortical thickness was calculated with Freesurfer. Upon subsequent autopsy, 12 cortical regions from the right and 9 from the left hemisphere were dissected and immunostained for amyloid-beta, p-tau, CD68 and C4b complement, and area %load was calculated. MRI-pathology associations were assessed with linear mixed models.
Results
A region-wide positive association between amyloid-beta load and cortical thickness was found in AD cases (r=0.17,p=0.012). In contrast, region-specific negative associations between p-tau and cortical thickness were found in frontal (r=-0.91,p<0.001), parietal (r=-0.71,p<0.001) and medial temporal regions (r=-0.89,p<0.001). CD68 load contributed to the correlation with cortical thickness in the parietal region even when controlling for p-tau (r=-0.55,p=0.048).
Conclusions
Our results show that amyloid-beta and p-tau burden contribute to cortical thickness differently: while amyloid-beta contributes to a cortical thickening diffusely, p-tau strongly contributes to cortical thinning in specific regions. Moreover, reactive microglia load contributes to cortical thinning in the inferior parietal gyrus, independently of the underlying pathology.