Associations of phosphorylated tau pathology with whole-hemisphere ex vivo morphometry in 7 tesla MRI.
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Sadaghiani Shokufeh, Trotman Winifred, Lim Sydney A, Chung Eunice, Ittyerah Ranjit, Ravikumar Sadhana, Khandelwal Pulkit, Prabhakaran Karthik, Lavery Madigan L, Ohm Daniel T, Gabrielyan Marianna, Das Sandhitsu R, Schuck Theresa, Capp Noah, Peterson Claire S, Migdal Elyse, Artacho-Pérula Emilio, Jiménez María Del Mar Arroyo, Rabal Maria Del Pilar Marcos, Sánchez Sandra Cebada, Prieto Carlos de la Rosa, Parada Marta Córcoles, Insausti Ricardo, Robinson John L, McMillan Corey, Grossman Murray, Lee Edward B, Detre John A, Xie Sharon X, Trojanowski John Q, Tisdall M Dylan, Wisse Laura E M, Irwin David J, Wolk David A, Yushkevich Paul A
Аннотация
METHODS: Thirty-three brain hemispheres from donors with an Alzheimer's disease (AD) spectrum diagnosis underwent T2-weighted magnetic resonance imaging (MRI). Gray matter thickness was paired with histopathology from the closest anatomic region in the contralateral hemisphere.
RESULTS: Partial Spearman correlation of phosphorylated tau and cortical thickness with TAR DNA-binding protein 43 (TDP-43) and α-synuclein scores, age, sex, and postmortem interval as covariates showed significant relationships in entorhinal and primary visual cortices, temporal pole, and insular and posterior cingulate gyri. Linear models including Braak stages, TDP-43 and α-synuclein scores, age, sex, and postmortem interval showed significant correlation between Braak stage and thickness in the parahippocampal gyrus, entorhinal cortex, and Broadman area 35.
CONCLUSION: We demonstrated an association of measures of AD pathology with tissue loss in several AD regions despite a limited range of pathology in these cases.
HIGHLIGHTS: Neurodegenerative disorders are associated with co-occurring pathologies that cannot be measured specifically with in vivo methods. Identification of the topographic patterns of these pathologies in structural magnetic resonance imaging (MRI) may provide probabilistic biomarkers. We demonstrated the correlation of the specific patterns of tissue loss from ex vivo brain MRI with underlying pathologies detected in postmortem brain hemispheres in patients with Alzheimer's disease (AD) spectrum disorders. The results provide insight into the interpretation of in vivo structural MRI studies in patients with AD spectrum disorders.