Linking histology to post‐mortem 7T MRI measures of neurodegeneration. (20th December 2022)

• Record Type: Journal Article
• Authors: Sadaghiani, Shokufeh; Ravikumar, Sadhana; Ittyerah, Ranjit; Lim, Sydney A; Chung, Eunice; Bedard, Madigan L; Xie, Long; Das, Sandhitsu R.; Schuck, Theresa; Grossman, Murray; Lee, Eddie B; Tisdall, Dylan M; Prabhakaran, Karthik; Detre, John A.; Mizsei, Gabor; Trojanowski, John Q; Irwin, David J.; Wisse, Laura EM; Wolk, David A.; Yushkevich, Paul A.
• Is Part Of: Alzheimer's & dementia. Volume 18(2022)Supplement 5
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-20
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.066155
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Neurodegenerative disorders are associated with different pathologies that often co‐occur and have differential contribution to the pattern of cognitive impairment. The majority of these pathologies cannot be detected or measured by in‐vivo methods; therefore, recognition of the topographic patterns of them and association with MRI findings may provide probabilistic non‐invasive biomarkers. We investigated the association of cortical and medial temporal lobe subregional thickness measured from postmortem MRI and semi‐quantitative pathologic measures in order to provide a methodological approach for linking pathological and radiological measures. Method: 22 brain hemispheres from donors with Alzheimer's disease (AD) spectrum diagnosis were included. T2‐weighted images were obtained on 7 Tesla scanner (0.28 mm isotropic) and patches of cortex around 16 anatomical locations were segmented using semi‐automated active contour segmentation in ITK‐SNAP. Immunohistochemistry evaluation was performed using previously validated antibodies to detect amyloid‐β, phosphorylated tau, phosphorylated TDP‐43 deposits and pathological conformation of α‐synuclein on contralateral hemispheres. Neuronal loss was visually assessed. Thickness measures at each location were associated with pathology measures at corresponding or closest to corresponding anatomical location. Multivariate linear models were used for statistical analyses. Result: The mean age of donors at death was 80.2±10.7 years (range 63‐99) and 8 (36%) were female. The median Braak stage was 5 (range: 2‐6). Linear models including regional Tau and TDP43 scores and age showed significant relationships between increased regional tau score and reduced thickness in anterior temporal pole, entorhinal, angular and superior parietal cortices. (Table 1, Figure 1) Linear models including Braak stages, TDP43 scores and age showed significant correlation between Braak stage and thickness in anterior temporal pole and entorhinal cortices and BA35 region of medial temporal lobe. Conclusion: The aim of the current study is to validate methods for development of 3D pathology maps which can be directly linked to local neurodegeneration measures. As the primary result of such an effort, the present study demonstrates an association of semi‐quantitative measures of AD pathology and with local tissue loss in several common AD regions despite limited range of pathology in these cases. These promising results provide support for future studies directly linking pathology with post‐mortem measures of structure.