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Preferential tau aggregation in von Economo neurons and fork cells in frontotemporal lobar degeneration with specific MAPT variants

Tau aggregation is a hallmark feature in a subset of patients with frontotemporal dementia (FTD). Early and selective loss of von Economo neurons (VENs) and fork cells within the frontoinsular (FI) and anterior cingulate cortices (ACC) is observed in patients with sporadic behavioral variant FTD (bv...

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Autores principales: Lin, Li-Chun, Nana, Alissa L., Hepker, Mackenzie, Hwang, Ji-Hye Lee, Gaus, Stephanie E., Spina, Salvatore, Cosme, Celica G., Gan, Li, Grinberg, Lea T., Geschwind, Daniel H., Coppola, Giovanni, Rosen, Howard J., Miller, Bruce L., Seeley, William W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805408/
https://www.ncbi.nlm.nih.gov/pubmed/31640778
http://dx.doi.org/10.1186/s40478-019-0809-0
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author Lin, Li-Chun
Nana, Alissa L.
Hepker, Mackenzie
Hwang, Ji-Hye Lee
Gaus, Stephanie E.
Spina, Salvatore
Cosme, Celica G.
Gan, Li
Grinberg, Lea T.
Geschwind, Daniel H.
Coppola, Giovanni
Rosen, Howard J.
Miller, Bruce L.
Seeley, William W.
author_facet Lin, Li-Chun
Nana, Alissa L.
Hepker, Mackenzie
Hwang, Ji-Hye Lee
Gaus, Stephanie E.
Spina, Salvatore
Cosme, Celica G.
Gan, Li
Grinberg, Lea T.
Geschwind, Daniel H.
Coppola, Giovanni
Rosen, Howard J.
Miller, Bruce L.
Seeley, William W.
author_sort Lin, Li-Chun
collection PubMed
description Tau aggregation is a hallmark feature in a subset of patients with frontotemporal dementia (FTD). Early and selective loss of von Economo neurons (VENs) and fork cells within the frontoinsular (FI) and anterior cingulate cortices (ACC) is observed in patients with sporadic behavioral variant FTD (bvFTD) due to frontotemporal lobar degeneration (FTLD), including FTLD with tau inclusions (FTLD-tau). Recently, we further showed that these specialized neurons show preferential aggregation of TDP-43 in FTLD-TDP. Whether VENs and fork cells are prone to tau accumulation in FTLD-tau remains unclear, and no previous studies of these neurons have focused on patients with pathogenic variants in the gene encoding microtubule-associated protein tau (FTLD-tau/MAPT). Here, we examined regional profiles of tau aggregation and neurodegeneration in 40 brain regions in 8 patients with FTLD-tau/MAPT and 7 with Pick’s disease (PiD), a sporadic form of FTLD-tau that often presents with bvFTD. We further qualitatively assessed the cellular patterns of frontoinsular tau aggregation in FTLD-tau/MAPT using antibodies specific for tau hyperphosphorylation, acetylation, or conformational change. ACC and mid-insula were among the regions most affected by neurodegeneration and tau aggregation in FTLD-tau/MAPT and PiD. In these two forms of FTLD-tau, severity of regional neurodegeneration and tau protein aggregation were highly correlated across regions. In FTLD-tau/MAPT, VENs and fork cells showed disproportionate tau protein aggregation in patients with V337 M, A152T, and IVS10 + 16 variants, but not in patients with the P301L variant. As seen in FTLD-TDP, our data suggest that VENs and fork cells represent preferentially vulnerable neuron types in most, but not all of the MAPT variants we studied.
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spelling pubmed-68054082019-10-24 Preferential tau aggregation in von Economo neurons and fork cells in frontotemporal lobar degeneration with specific MAPT variants Lin, Li-Chun Nana, Alissa L. Hepker, Mackenzie Hwang, Ji-Hye Lee Gaus, Stephanie E. Spina, Salvatore Cosme, Celica G. Gan, Li Grinberg, Lea T. Geschwind, Daniel H. Coppola, Giovanni Rosen, Howard J. Miller, Bruce L. Seeley, William W. Acta Neuropathol Commun Research Tau aggregation is a hallmark feature in a subset of patients with frontotemporal dementia (FTD). Early and selective loss of von Economo neurons (VENs) and fork cells within the frontoinsular (FI) and anterior cingulate cortices (ACC) is observed in patients with sporadic behavioral variant FTD (bvFTD) due to frontotemporal lobar degeneration (FTLD), including FTLD with tau inclusions (FTLD-tau). Recently, we further showed that these specialized neurons show preferential aggregation of TDP-43 in FTLD-TDP. Whether VENs and fork cells are prone to tau accumulation in FTLD-tau remains unclear, and no previous studies of these neurons have focused on patients with pathogenic variants in the gene encoding microtubule-associated protein tau (FTLD-tau/MAPT). Here, we examined regional profiles of tau aggregation and neurodegeneration in 40 brain regions in 8 patients with FTLD-tau/MAPT and 7 with Pick’s disease (PiD), a sporadic form of FTLD-tau that often presents with bvFTD. We further qualitatively assessed the cellular patterns of frontoinsular tau aggregation in FTLD-tau/MAPT using antibodies specific for tau hyperphosphorylation, acetylation, or conformational change. ACC and mid-insula were among the regions most affected by neurodegeneration and tau aggregation in FTLD-tau/MAPT and PiD. In these two forms of FTLD-tau, severity of regional neurodegeneration and tau protein aggregation were highly correlated across regions. In FTLD-tau/MAPT, VENs and fork cells showed disproportionate tau protein aggregation in patients with V337 M, A152T, and IVS10 + 16 variants, but not in patients with the P301L variant. As seen in FTLD-TDP, our data suggest that VENs and fork cells represent preferentially vulnerable neuron types in most, but not all of the MAPT variants we studied. BioMed Central 2019-10-22 /pmc/articles/PMC6805408/ /pubmed/31640778 http://dx.doi.org/10.1186/s40478-019-0809-0 Text en © The Author(s). 2019 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. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Lin, Li-Chun
Nana, Alissa L.
Hepker, Mackenzie
Hwang, Ji-Hye Lee
Gaus, Stephanie E.
Spina, Salvatore
Cosme, Celica G.
Gan, Li
Grinberg, Lea T.
Geschwind, Daniel H.
Coppola, Giovanni
Rosen, Howard J.
Miller, Bruce L.
Seeley, William W.
Preferential tau aggregation in von Economo neurons and fork cells in frontotemporal lobar degeneration with specific MAPT variants
title Preferential tau aggregation in von Economo neurons and fork cells in frontotemporal lobar degeneration with specific MAPT variants
title_full Preferential tau aggregation in von Economo neurons and fork cells in frontotemporal lobar degeneration with specific MAPT variants
title_fullStr Preferential tau aggregation in von Economo neurons and fork cells in frontotemporal lobar degeneration with specific MAPT variants
title_full_unstemmed Preferential tau aggregation in von Economo neurons and fork cells in frontotemporal lobar degeneration with specific MAPT variants
title_short Preferential tau aggregation in von Economo neurons and fork cells in frontotemporal lobar degeneration with specific MAPT variants
title_sort preferential tau aggregation in von economo neurons and fork cells in frontotemporal lobar degeneration with specific mapt variants
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805408/
https://www.ncbi.nlm.nih.gov/pubmed/31640778
http://dx.doi.org/10.1186/s40478-019-0809-0
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