Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions

Wisse, L. E.M. LU orcid ; Ravikumar, S. ; Ittyerah, R. ; Lim, S. ; Lane, J. ; Bedard, M. L. ; Xie, L. ; Das, S. R. ; Schuck, T. and Grossman, M. , et al. (2021) In Acta Neuropathologica Communications 9(1).
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)... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Acta Neuropathologica Communications
volume
9
issue
1
article number
128
publisher
BioMed Central (BMC)
external identifiers
  • pmid:34289895
  • scopus:85112053619
ISSN
2051-5960
DOI
10.1186/s40478-021-01225-3
language
English
LU publication?
yes
id
7a7e62eb-52cb-4bba-aa46-daf707b85106
date added to LUP
2021-09-03 14:04:49
date last changed
2025-03-10 20:54:39
@article{7a7e62eb-52cb-4bba-aa46-daf707b85106,
  abstract     = {{<p>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 mm<sup>3</sup> 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.</p>}},
  author       = {{Wisse, L. E.M. and Ravikumar, S. and Ittyerah, R. and Lim, S. and Lane, J. and Bedard, M. L. and Xie, L. and Das, S. R. and Schuck, T. and Grossman, M. and Lee, E. B. and Tisdall, M. D. and Prabhakaran, K. and Detre, J. A. and Mizsei, G. and Trojanowski, J. Q. and Artacho-Pérula, E. and de Iñiguez de Onzono Martin, M. M. and M. Arroyo-Jiménez, M. and Muñoz Lopez, M. and Molina Romero, F. J. and P. Marcos Rabal, M. and Cebada Sánchez, S. and Delgado González, J. C. and de la Rosa Prieto, C. and Córcoles Parada, M. and Wolk, D. A. and Irwin, D. J. and Insausti, R. and Yushkevich, P. A.}},
  issn         = {{2051-5960}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Acta Neuropathologica Communications}},
  title        = {{Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions}},
  url          = {{http://dx.doi.org/10.1186/s40478-021-01225-3}},
  doi          = {{10.1186/s40478-021-01225-3}},
  volume       = {{9}},
  year         = {{2021}},
}