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Associations of phosphorylated tau pathology with whole-hemisphere ex vivo morphometry in 7 tesla MRI

Sadaghiani, Shokufeh ; Trotman, Winifred ; Lim, Sydney A. ; Chung, Eunice ; Ittyerah, Ranjit ; Ravikumar, Sadhana ; Khandelwal, Pulkit ; Prabhakaran, Karthik ; Lavery, Madigan L. and Ohm, Daniel T. , et al. (2023) In Alzheimer's and Dementia 19(6). p.2355-2364
Abstract

Introduction: Neurodegenerative disorders are associated with different pathologies that often co-occur but cannot be measured specifically with in vivo methods. 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... (More)

Introduction: Neurodegenerative disorders are associated with different pathologies that often co-occur but cannot be measured specifically with in vivo methods. 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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, biomarkers, cortical thickness, ex vivo MRI, neurodegeneration
in
Alzheimer's and Dementia
volume
19
issue
6
pages
10 pages
publisher
Wiley
external identifiers
  • pmid:36464907
  • scopus:85143989842
ISSN
1552-5260
DOI
10.1002/alz.12884
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2022 the Alzheimer's Association.
id
99df6d12-fd35-4a3a-a59b-58ffd1a69321
date added to LUP
2023-10-09 10:36:52
date last changed
2024-04-19 02:06:06
@article{99df6d12-fd35-4a3a-a59b-58ffd1a69321,
  abstract     = {{<p>Introduction: Neurodegenerative disorders are associated with different pathologies that often co-occur but cannot be measured specifically with in vivo methods. 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.</p>}},
  author       = {{Sadaghiani, Shokufeh and Trotman, Winifred and Lim, Sydney A. and Chung, Eunice and Ittyerah, Ranjit and Ravikumar, Sadhana and Khandelwal, Pulkit and Prabhakaran, Karthik and Lavery, Madigan L. and Ohm, Daniel T. and Gabrielyan, Marianna and Das, Sandhitsu R. and Schuck, Theresa and Capp, Noah and Peterson, Claire S. and Migdal, Elyse and Artacho-Pérula, Emilio and Jiménez, María del Mar Arroyo and Rabal, Maria del Pilar Marcos and Sánchez, Sandra Cebada and Prieto, Carlos de la Rosa and Parada, Marta Córcoles and Insausti, Ricardo and Robinson, John L. and McMillan, Corey and Grossman, Murray and Lee, Edward B. and Detre, John A. and Xie, Sharon X. and Trojanowski, John Q. and Tisdall, M. Dylan and Wisse, Laura E.M. and Irwin, David J. and Wolk, David A. and Yushkevich, Paul A.}},
  issn         = {{1552-5260}},
  keywords     = {{Alzheimer's disease; biomarkers; cortical thickness; ex vivo MRI; neurodegeneration}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{2355--2364}},
  publisher    = {{Wiley}},
  series       = {{Alzheimer's and Dementia}},
  title        = {{Associations of phosphorylated tau pathology with whole-hemisphere ex vivo morphometry in 7 tesla MRI}},
  url          = {{http://dx.doi.org/10.1002/alz.12884}},
  doi          = {{10.1002/alz.12884}},
  volume       = {{19}},
  year         = {{2023}},
}