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Ex vivo MRI atlas of the human medial temporal lobe : characterizing neurodegeneration due to tau pathology

Ravikumar, Sadhana ; Wisse, Laura E.M. LU orcid ; Lim, Sydney ; Ittyerah, Ranjit ; Xie, Long ; Bedard, Madigan L. ; Das, Sandhitsu R. ; Lee, Edward B. ; Tisdall, M. Dylan and Prabhakaran, Karthik , et al. (2021) In Acta Neuropathologica Communications 9(1).
Abstract

Tau neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimer’s disease (AD). To elucidate patterns of structural change in the MTL specifically associated with tau pathology, we compared high-resolution ex vivo MRI scans of human postmortem MTL specimens with histology-based pathological assessments of the MTL. MTL specimens were obtained from twenty-nine brain donors, including patients with AD, other dementias, and individuals with no known history of neurological disease. Ex vivo MRI scans were combined using a customized groupwise diffeomorphic registration approach to construct a 3D probabilistic atlas that... (More)

Tau neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimer’s disease (AD). To elucidate patterns of structural change in the MTL specifically associated with tau pathology, we compared high-resolution ex vivo MRI scans of human postmortem MTL specimens with histology-based pathological assessments of the MTL. MTL specimens were obtained from twenty-nine brain donors, including patients with AD, other dementias, and individuals with no known history of neurological disease. Ex vivo MRI scans were combined using a customized groupwise diffeomorphic registration approach to construct a 3D probabilistic atlas that captures the anatomical variability of the MTL. Using serial histology imaging in eleven specimens, we labelled the MTL subregions in the atlas based on cytoarchitecture. Leveraging the atlas and neuropathological ratings of tau and TAR DNA-binding protein 43 (TDP-43) pathology severity, morphometric analysis was performed to correlate regional MTL thickness with the severity of tau pathology, after correcting for age and TDP-43 pathology. We found significant correlations between tau pathology and thickness in the entorhinal cortex (ERC) and stratum radiatum lacunosum moleculare (SRLM). When focusing on cases with low levels of TDP-43 pathology, we found strong associations between tau pathology and thickness in the ERC, SRLM and the subiculum/cornu ammonis 1 (CA1) subfields of the hippocampus, consistent with early Braak stages.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer’s disease, Biomarkers, Co-morbidities, Ex vivo MRI, Neurodegeneration, Neurofibrillary tangles
in
Acta Neuropathologica Communications
volume
9
issue
1
article number
173
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85117858013
  • pmid:34689831
ISSN
2051-5960
DOI
10.1186/s40478-021-01275-7
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2021, The Author(s).
id
fb8f98ff-dc7b-4373-8311-bf0772686acf
date added to LUP
2021-11-22 13:03:42
date last changed
2024-04-06 13:43:52
@article{fb8f98ff-dc7b-4373-8311-bf0772686acf,
  abstract     = {{<p>Tau neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimer’s disease (AD). To elucidate patterns of structural change in the MTL specifically associated with tau pathology, we compared high-resolution ex vivo MRI scans of human postmortem MTL specimens with histology-based pathological assessments of the MTL. MTL specimens were obtained from twenty-nine brain donors, including patients with AD, other dementias, and individuals with no known history of neurological disease. Ex vivo MRI scans were combined using a customized groupwise diffeomorphic registration approach to construct a 3D probabilistic atlas that captures the anatomical variability of the MTL. Using serial histology imaging in eleven specimens, we labelled the MTL subregions in the atlas based on cytoarchitecture. Leveraging the atlas and neuropathological ratings of tau and TAR DNA-binding protein 43 (TDP-43) pathology severity, morphometric analysis was performed to correlate regional MTL thickness with the severity of tau pathology, after correcting for age and TDP-43 pathology. We found significant correlations between tau pathology and thickness in the entorhinal cortex (ERC) and stratum radiatum lacunosum moleculare (SRLM). When focusing on cases with low levels of TDP-43 pathology, we found strong associations between tau pathology and thickness in the ERC, SRLM and the subiculum/cornu ammonis 1 (CA1) subfields of the hippocampus, consistent with early Braak stages.</p>}},
  author       = {{Ravikumar, Sadhana and Wisse, Laura E.M. and Lim, Sydney and Ittyerah, Ranjit and Xie, Long and Bedard, Madigan L. and Das, Sandhitsu R. and Lee, Edward B. and Tisdall, M. Dylan and Prabhakaran, Karthik and Lane, Jacqueline and Detre, John A. and Mizsei, Gabor and Trojanowski, John Q. and Robinson, John L. and Schuck, Theresa and Grossman, Murray and Artacho-Pérula, Emilio and de Onzoño Martin, Maria Mercedes Iñiguez and del Mar Arroyo Jiménez, María and Muñoz, Monica and Romero, Francisco Javier Molina and del Pilar Marcos Rabal, Maria and Sánchez, Sandra Cebada and González, José Carlos Delgado and de la Rosa Prieto, Carlos and Parada, Marta Córcoles and Irwin, David J. and Wolk, David A. and Insausti, Ricardo and Yushkevich, Paul A.}},
  issn         = {{2051-5960}},
  keywords     = {{Alzheimer’s disease; Biomarkers; Co-morbidities; Ex vivo MRI; Neurodegeneration; Neurofibrillary tangles}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Acta Neuropathologica Communications}},
  title        = {{Ex vivo MRI atlas of the human medial temporal lobe : characterizing neurodegeneration due to tau pathology}},
  url          = {{http://dx.doi.org/10.1186/s40478-021-01275-7}},
  doi          = {{10.1186/s40478-021-01275-7}},
  volume       = {{9}},
  year         = {{2021}},
}