Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions
Abstract The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post...
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BMC
2021-07-01
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Series: | Acta Neuropathologica Communications |
Online Access: | https://doi.org/10.1186/s40478-021-01225-3 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
L. E. M. Wisse S. Ravikumar R. Ittyerah S. Lim J. Lane M. L. Bedard L. Xie S. R. Das T. Schuck M. Grossman E. B. Lee M. D. Tisdall K. Prabhakaran J. A. Detre G. Mizsei J. Q. Trojanowski E. Artacho-Pérula M. M. de Iñiguez de Onzono Martin M. M. Arroyo-Jiménez M. Muñoz Lopez F. J. Molina Romero M. P. Marcos Rabal S. Cebada Sánchez J. C. Delgado González C. de la Rosa Prieto M. Córcoles Parada D. A. Wolk D. J. Irwin R. Insausti P. A. Yushkevich |
spellingShingle |
L. E. M. Wisse S. Ravikumar R. Ittyerah S. Lim J. Lane M. L. Bedard L. Xie S. R. Das T. Schuck M. Grossman E. B. Lee M. D. Tisdall K. Prabhakaran J. A. Detre G. Mizsei J. Q. Trojanowski E. Artacho-Pérula M. M. de Iñiguez de Onzono Martin M. M. Arroyo-Jiménez M. Muñoz Lopez F. J. Molina Romero M. P. Marcos Rabal S. Cebada Sánchez J. C. Delgado González C. de la Rosa Prieto M. Córcoles Parada D. A. Wolk D. J. Irwin R. Insausti P. A. Yushkevich Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions Acta Neuropathologica Communications |
author_facet |
L. E. M. Wisse S. Ravikumar R. Ittyerah S. Lim J. Lane M. L. Bedard L. Xie S. R. Das T. Schuck M. Grossman E. B. Lee M. D. Tisdall K. Prabhakaran J. A. Detre G. Mizsei J. Q. Trojanowski E. Artacho-Pérula M. M. de Iñiguez de Onzono Martin M. M. Arroyo-Jiménez M. Muñoz Lopez F. J. Molina Romero M. P. Marcos Rabal S. Cebada Sánchez J. C. Delgado González C. de la Rosa Prieto M. Córcoles Parada D. A. Wolk D. J. Irwin R. Insausti P. A. Yushkevich |
author_sort |
L. E. M. Wisse |
title |
Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions |
title_short |
Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions |
title_full |
Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions |
title_fullStr |
Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions |
title_full_unstemmed |
Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions |
title_sort |
downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions |
publisher |
BMC |
series |
Acta Neuropathologica Communications |
issn |
2051-5960 |
publishDate |
2021-07-01 |
description |
Abstract The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-β and α-synuclein pathology were rated on a scale of 0 (absent)—3 (severe) in the hippocampus and entorhinal cortex (ERC) of 58 individuals with and without neurodegenerative diseases (median age 75.0 years, 60.3% male). Thickness measurements in ERC, Brodmann Area (BA) 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare (SRLM) were derived from 0.2 × 0.2 × 0.2 mm3 post-mortem MRI scans of excised MTL specimens from the contralateral hemisphere using a semi-automated approach. Spearman’s rank correlations were performed between neurodegenerative pathologies and thickness, correcting for age, sex and hemisphere, including all four proteinopathies in the model. We found significant associations of (1) TDP-43 with thickness in all subregions (r = − 0.27 to r = − 0.46), and (2) tau with BA35 (r = − 0.31) and SRLM thickness (r = − 0.33). In amyloid-β and TDP-43 negative cases, we found strong significant associations of tau with ERC (r = − 0.40), BA35 (r = − 0.55), subiculum (r = − 0.42) and CA1 thickness (r = − 0.47). This unique dataset shows widespread MTL atrophy in relation to TDP-43 pathology and atrophy in regions affected early in Braak stageing and tau pathology. Moreover, the strong association of tau with thickness in early Braak regions in the absence of amyloid-β suggests a role of Primary Age-Related Tauopathy in neurodegeneration. |
url |
https://doi.org/10.1186/s40478-021-01225-3 |
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doaj-a1f724ff19b546a29d9da05b0ce5aed22021-07-25T11:10:00ZengBMCActa Neuropathologica Communications2051-59602021-07-019111110.1186/s40478-021-01225-3Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregionsL. E. M. Wisse0S. Ravikumar1R. Ittyerah2S. Lim3J. Lane4M. L. Bedard5L. Xie6S. R. Das7T. Schuck8M. Grossman9E. B. Lee10M. D. Tisdall11K. Prabhakaran12J. A. Detre13G. Mizsei14J. Q. Trojanowski15E. Artacho-Pérula16M. M. de Iñiguez de Onzono Martin17M. M. Arroyo-Jiménez18M. Muñoz Lopez19F. J. Molina Romero20M. P. Marcos Rabal21S. Cebada Sánchez22J. C. Delgado González23C. de la Rosa Prieto24M. Córcoles Parada25D. A. Wolk26D. J. Irwin27R. Insausti28P. A. Yushkevich29Department of Diagnostic Radiology, Lund UniversityDepartment of Radiology, University of PennsylvaniaDepartment of Radiology, University of PennsylvaniaDepartment of Radiology, University of PennsylvaniaDepartment of Neurology, University of PennsylvaniaDepartment of Pharmacology, University of North Carolina At Chapel HillDepartment of Radiology, University of PennsylvaniaDepartment of Neurology, University of PennsylvaniaCenter for Neurodegenerative Disease Research, University of PennsylvaniaDepartment of Neurology, University of PennsylvaniaCenter for Neurodegenerative Disease Research, University of PennsylvaniaDepartment of Radiology, University of PennsylvaniaDepartment of Neurology, University of PennsylvaniaDepartment of Neurology, University of PennsylvaniaDepartment of Radiology, University of PennsylvaniaCenter for Neurodegenerative Disease Research, University of PennsylvaniaHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La ManchaHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La ManchaHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La ManchaHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La ManchaHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La ManchaHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La ManchaHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La ManchaHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La ManchaHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La ManchaHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La ManchaDepartment of Neurology, University of PennsylvaniaDepartment of Neurology, University of PennsylvaniaHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La ManchaDepartment of Radiology, University of PennsylvaniaAbstract The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-β and α-synuclein pathology were rated on a scale of 0 (absent)—3 (severe) in the hippocampus and entorhinal cortex (ERC) of 58 individuals with and without neurodegenerative diseases (median age 75.0 years, 60.3% male). Thickness measurements in ERC, Brodmann Area (BA) 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare (SRLM) were derived from 0.2 × 0.2 × 0.2 mm3 post-mortem MRI scans of excised MTL specimens from the contralateral hemisphere using a semi-automated approach. Spearman’s rank correlations were performed between neurodegenerative pathologies and thickness, correcting for age, sex and hemisphere, including all four proteinopathies in the model. We found significant associations of (1) TDP-43 with thickness in all subregions (r = − 0.27 to r = − 0.46), and (2) tau with BA35 (r = − 0.31) and SRLM thickness (r = − 0.33). In amyloid-β and TDP-43 negative cases, we found strong significant associations of tau with ERC (r = − 0.40), BA35 (r = − 0.55), subiculum (r = − 0.42) and CA1 thickness (r = − 0.47). This unique dataset shows widespread MTL atrophy in relation to TDP-43 pathology and atrophy in regions affected early in Braak stageing and tau pathology. Moreover, the strong association of tau with thickness in early Braak regions in the absence of amyloid-β suggests a role of Primary Age-Related Tauopathy in neurodegeneration.https://doi.org/10.1186/s40478-021-01225-3 |