Quantitative neuropathology: an update on automated methodologies and implications for large scale cohorts

A tissue microarray (TMA) has previously been developed for use in assessment of neurodegenerative diseases. We investigated the variation of pathology loads in semi-quantitative score categories and how pathology load related to disease progression. Post-mortem tissue from 146 cases were used; Alzh...

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Autores principales: Walker, Lauren, McAleese, Kirsty E., Johnson, Mary, Khundakar, Ahmad A., Erskine, Daniel, Thomas, Alan J., McKeith, Ian G., Attems, Johannes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Vienna 2017
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446847/
https://www.ncbi.nlm.nih.gov/pubmed/28265813
http://dx.doi.org/10.1007/s00702-017-1702-2
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author Walker, Lauren
McAleese, Kirsty E.
Johnson, Mary
Khundakar, Ahmad A.
Erskine, Daniel
Thomas, Alan J.
McKeith, Ian G.
Attems, Johannes
author_facet Walker, Lauren
McAleese, Kirsty E.
Johnson, Mary
Khundakar, Ahmad A.
Erskine, Daniel
Thomas, Alan J.
McKeith, Ian G.
Attems, Johannes
author_sort Walker, Lauren
collection PubMed
description A tissue microarray (TMA) has previously been developed for use in assessment of neurodegenerative diseases. We investigated the variation of pathology loads in semi-quantitative score categories and how pathology load related to disease progression. Post-mortem tissue from 146 cases were used; Alzheimer’s disease (AD) (n = 36), Lewy body disease (LBD) (n = 56), mixed AD/dementia with Lewy bodies (n = 14) and controls (n = 40). TMA blocks (one per case) were constructed using tissue cores from 15 brain regions including cortical and subcortical regions. TMA tissue sections were stained for hyperphosphorylated tau (HP-(T)), β amyloid and α-synuclein (αsyn), and quantified using an automated image analysis system. Cases classified as Braak stage VI displayed a wide variation in HP-(T) pathology in the entorhinal cortex (interquartile range 4.13–44.03%). The interquartile range for β amyloid in frontal cortex in cases classified as Thal phase 5 was 6.75–17.03% and for αsyn in the cingulate in cases classified as McKeith neocortical LBD was 0.04–0.58%. In AD and control cases, HP-(T) load predicted the Braak stage (p < 0.001), β amyloid load predicted Thal phase (p < 0.001) and αsyn load in LBD cases predicted McKeith type of LBD (p < 0.001). Quantitative data from TMA assessment highlight the range in pathological load across cases classified with ‘severe’ pathology and is beneficial to further elucidate the heterogeneity of neurodegenerative diseases. Quantifying pathology in multiple brain regions may allow identification of novel clinico-pathological phenotypes for the improvement of intra vitam stratification of clinical cohorts according to underlying pathologies.
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spelling pubmed-54468472017-06-06 Quantitative neuropathology: an update on automated methodologies and implications for large scale cohorts Walker, Lauren McAleese, Kirsty E. Johnson, Mary Khundakar, Ahmad A. Erskine, Daniel Thomas, Alan J. McKeith, Ian G. Attems, Johannes J Neural Transm (Vienna) Translational Neurosciences - Original Article A tissue microarray (TMA) has previously been developed for use in assessment of neurodegenerative diseases. We investigated the variation of pathology loads in semi-quantitative score categories and how pathology load related to disease progression. Post-mortem tissue from 146 cases were used; Alzheimer’s disease (AD) (n = 36), Lewy body disease (LBD) (n = 56), mixed AD/dementia with Lewy bodies (n = 14) and controls (n = 40). TMA blocks (one per case) were constructed using tissue cores from 15 brain regions including cortical and subcortical regions. TMA tissue sections were stained for hyperphosphorylated tau (HP-(T)), β amyloid and α-synuclein (αsyn), and quantified using an automated image analysis system. Cases classified as Braak stage VI displayed a wide variation in HP-(T) pathology in the entorhinal cortex (interquartile range 4.13–44.03%). The interquartile range for β amyloid in frontal cortex in cases classified as Thal phase 5 was 6.75–17.03% and for αsyn in the cingulate in cases classified as McKeith neocortical LBD was 0.04–0.58%. In AD and control cases, HP-(T) load predicted the Braak stage (p < 0.001), β amyloid load predicted Thal phase (p < 0.001) and αsyn load in LBD cases predicted McKeith type of LBD (p < 0.001). Quantitative data from TMA assessment highlight the range in pathological load across cases classified with ‘severe’ pathology and is beneficial to further elucidate the heterogeneity of neurodegenerative diseases. Quantifying pathology in multiple brain regions may allow identification of novel clinico-pathological phenotypes for the improvement of intra vitam stratification of clinical cohorts according to underlying pathologies. Springer Vienna 2017-03-06 2017 /pmc/articles/PMC5446847/ /pubmed/28265813 http://dx.doi.org/10.1007/s00702-017-1702-2 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Translational Neurosciences - Original Article
Walker, Lauren
McAleese, Kirsty E.
Johnson, Mary
Khundakar, Ahmad A.
Erskine, Daniel
Thomas, Alan J.
McKeith, Ian G.
Attems, Johannes
Quantitative neuropathology: an update on automated methodologies and implications for large scale cohorts
title Quantitative neuropathology: an update on automated methodologies and implications for large scale cohorts
title_full Quantitative neuropathology: an update on automated methodologies and implications for large scale cohorts
title_fullStr Quantitative neuropathology: an update on automated methodologies and implications for large scale cohorts
title_full_unstemmed Quantitative neuropathology: an update on automated methodologies and implications for large scale cohorts
title_short Quantitative neuropathology: an update on automated methodologies and implications for large scale cohorts
title_sort quantitative neuropathology: an update on automated methodologies and implications for large scale cohorts
topic Translational Neurosciences - Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446847/
https://www.ncbi.nlm.nih.gov/pubmed/28265813
http://dx.doi.org/10.1007/s00702-017-1702-2
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