Asymmetric TDP pathology in primary progressive aphasia with right hemisphere language dominance

Garam Kim, Shahrooz Vahedi, Tamar Devora Gefen, Sandra Weintraub, Eileen H Bigio, Marek-Marsel Mesulam, Changiz Geula*

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective To quantitatively examine the regional densities and hemispheric distribution of the 43-kDa transactive response DNA-binding protein (TDP-43) inclusions, neurons, and activated microglia in a left-handed patient with right hemisphere language dominance and logopenic-variant primary progressive aphasia (PPA). Methods Phosphorylated TDP-43 inclusions, neurons, and activated microglia were visualized with immunohistochemical and histologic methods. Markers were quantified bilaterally with unbiased stereology in language-and memory-related cortical regions. Results Clinical MRI indicated cortical atrophy in the right hemisphere, mostly in the temporal lobe. Significantly higher densities of TDP-43 inclusions were present in right language-related temporal regions compared to the left or to other right hemisphere regions. The memory-related entorhinal cortex (ERC) and language regions without significant atrophy showed no asymmetry. Activated microglia displayed extensive asymmetry (R > L). A substantial density of neurons remained in all areas and showed no hemispheric asymmetry. However, perikaryal size was significantly smaller in the right hemisphere across all regions except the ERC. To demonstrate the specificity of this finding, sizes of residual neurons were measured in a right-handed case with PPA and were found to be smaller in the language-dominant left hemisphere. Conclusions The distribution of TDP-43 inclusions and microglial activation in right temporal language regions showed concordance with anatomic distribution of cortical atrophy and clinical presentation. The results revealed no direct relationship between density of TDP-43 inclusions and activated microglia. Reduced size of the remaining neurons is likely to contribute to cortical atrophy detected by MRI. These findings support the conclusion that there is no obligatory relationship between logopenic PPA and Alzheimer pathology.

Original languageEnglish (US)
Pages (from-to)e396-e403
JournalNeurology
Volume90
Issue number5
DOIs
StatePublished - Jan 30 2018

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Primary Progressive Aphasia
Language
Microglia
Pathology
Atrophy
Neurons
Temporal Lobe
Entorhinal Cortex
DNA-Binding Proteins
Patient Rights

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

@article{78514b0f5ee54fcc8aa88d1cae51ae7c,
title = "Asymmetric TDP pathology in primary progressive aphasia with right hemisphere language dominance",
abstract = "Objective To quantitatively examine the regional densities and hemispheric distribution of the 43-kDa transactive response DNA-binding protein (TDP-43) inclusions, neurons, and activated microglia in a left-handed patient with right hemisphere language dominance and logopenic-variant primary progressive aphasia (PPA). Methods Phosphorylated TDP-43 inclusions, neurons, and activated microglia were visualized with immunohistochemical and histologic methods. Markers were quantified bilaterally with unbiased stereology in language-and memory-related cortical regions. Results Clinical MRI indicated cortical atrophy in the right hemisphere, mostly in the temporal lobe. Significantly higher densities of TDP-43 inclusions were present in right language-related temporal regions compared to the left or to other right hemisphere regions. The memory-related entorhinal cortex (ERC) and language regions without significant atrophy showed no asymmetry. Activated microglia displayed extensive asymmetry (R > L). A substantial density of neurons remained in all areas and showed no hemispheric asymmetry. However, perikaryal size was significantly smaller in the right hemisphere across all regions except the ERC. To demonstrate the specificity of this finding, sizes of residual neurons were measured in a right-handed case with PPA and were found to be smaller in the language-dominant left hemisphere. Conclusions The distribution of TDP-43 inclusions and microglial activation in right temporal language regions showed concordance with anatomic distribution of cortical atrophy and clinical presentation. The results revealed no direct relationship between density of TDP-43 inclusions and activated microglia. Reduced size of the remaining neurons is likely to contribute to cortical atrophy detected by MRI. These findings support the conclusion that there is no obligatory relationship between logopenic PPA and Alzheimer pathology.",
author = "Garam Kim and Shahrooz Vahedi and Gefen, {Tamar Devora} and Sandra Weintraub and Bigio, {Eileen H} and Marek-Marsel Mesulam and Changiz Geula",
year = "2018",
month = "1",
day = "30",
doi = "10.1212/WNL.0000000000004891",
language = "English (US)",
volume = "90",
pages = "e396--e403",
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TY - JOUR

T1 - Asymmetric TDP pathology in primary progressive aphasia with right hemisphere language dominance

AU - Kim, Garam

AU - Vahedi, Shahrooz

AU - Gefen, Tamar Devora

AU - Weintraub, Sandra

AU - Bigio, Eileen H

AU - Mesulam, Marek-Marsel

AU - Geula, Changiz

PY - 2018/1/30

Y1 - 2018/1/30

N2 - Objective To quantitatively examine the regional densities and hemispheric distribution of the 43-kDa transactive response DNA-binding protein (TDP-43) inclusions, neurons, and activated microglia in a left-handed patient with right hemisphere language dominance and logopenic-variant primary progressive aphasia (PPA). Methods Phosphorylated TDP-43 inclusions, neurons, and activated microglia were visualized with immunohistochemical and histologic methods. Markers were quantified bilaterally with unbiased stereology in language-and memory-related cortical regions. Results Clinical MRI indicated cortical atrophy in the right hemisphere, mostly in the temporal lobe. Significantly higher densities of TDP-43 inclusions were present in right language-related temporal regions compared to the left or to other right hemisphere regions. The memory-related entorhinal cortex (ERC) and language regions without significant atrophy showed no asymmetry. Activated microglia displayed extensive asymmetry (R > L). A substantial density of neurons remained in all areas and showed no hemispheric asymmetry. However, perikaryal size was significantly smaller in the right hemisphere across all regions except the ERC. To demonstrate the specificity of this finding, sizes of residual neurons were measured in a right-handed case with PPA and were found to be smaller in the language-dominant left hemisphere. Conclusions The distribution of TDP-43 inclusions and microglial activation in right temporal language regions showed concordance with anatomic distribution of cortical atrophy and clinical presentation. The results revealed no direct relationship between density of TDP-43 inclusions and activated microglia. Reduced size of the remaining neurons is likely to contribute to cortical atrophy detected by MRI. These findings support the conclusion that there is no obligatory relationship between logopenic PPA and Alzheimer pathology.

AB - Objective To quantitatively examine the regional densities and hemispheric distribution of the 43-kDa transactive response DNA-binding protein (TDP-43) inclusions, neurons, and activated microglia in a left-handed patient with right hemisphere language dominance and logopenic-variant primary progressive aphasia (PPA). Methods Phosphorylated TDP-43 inclusions, neurons, and activated microglia were visualized with immunohistochemical and histologic methods. Markers were quantified bilaterally with unbiased stereology in language-and memory-related cortical regions. Results Clinical MRI indicated cortical atrophy in the right hemisphere, mostly in the temporal lobe. Significantly higher densities of TDP-43 inclusions were present in right language-related temporal regions compared to the left or to other right hemisphere regions. The memory-related entorhinal cortex (ERC) and language regions without significant atrophy showed no asymmetry. Activated microglia displayed extensive asymmetry (R > L). A substantial density of neurons remained in all areas and showed no hemispheric asymmetry. However, perikaryal size was significantly smaller in the right hemisphere across all regions except the ERC. To demonstrate the specificity of this finding, sizes of residual neurons were measured in a right-handed case with PPA and were found to be smaller in the language-dominant left hemisphere. Conclusions The distribution of TDP-43 inclusions and microglial activation in right temporal language regions showed concordance with anatomic distribution of cortical atrophy and clinical presentation. The results revealed no direct relationship between density of TDP-43 inclusions and activated microglia. Reduced size of the remaining neurons is likely to contribute to cortical atrophy detected by MRI. These findings support the conclusion that there is no obligatory relationship between logopenic PPA and Alzheimer pathology.

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