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Neuropathologic analysis of Tyr69His TTR variant meningovascular amyloidosis with dementia
Transthyretin/TTR gene mutations usually cause systemic amyloidotic diseases. Few TTR variants preferentially affect the central nervous system, manifesting as oculoleptomeningeal amyloidosis. Patients with TTR meningovascular amyloidosis often show dementia, however the neuropathologic features of...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496870/ https://www.ncbi.nlm.nih.gov/pubmed/26156087 http://dx.doi.org/10.1186/s40478-015-0216-0 |
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author | Ziskin, Jennifer L. Greicius, Michael D. Zhu, Wan Okumu, Anna N. Adams, Christopher M. Plowey, Edward D. |
author_facet | Ziskin, Jennifer L. Greicius, Michael D. Zhu, Wan Okumu, Anna N. Adams, Christopher M. Plowey, Edward D. |
author_sort | Ziskin, Jennifer L. |
collection | PubMed |
description | Transthyretin/TTR gene mutations usually cause systemic amyloidotic diseases. Few TTR variants preferentially affect the central nervous system, manifesting as oculoleptomeningeal amyloidosis. Patients with TTR meningovascular amyloidosis often show dementia, however the neuropathologic features of dementia in these cases have not been elucidated. We report the neuropathologic findings from a brain autopsy of a 72-year-old man with the rare Tyr69His (Y69H) TTR gene variant, dementia and ataxia. Severe amyloid deposits were observed in the leptomeninges and in a subpial and subependymal distribution. Mass spectrometry analysis demonstrated that the amyloid deposits were comprised of over 80 % of the variant TTR. TTR was undetectable by mass spectrometry in the neocortex subjacent to the subpial amyloid deposits. Subpial TTR amyloid deposits were associated with brisk superficial reactive gliosis and siderosis in the neocortex and cerebellar cortex. Subependymal TTR amyloid deposits were associated with subjacent myelin pallor in the hippocampal outflow tract structures including the alveus, fimbria and fornix. Phospho-tau immunostains demonstrated transentorhinal-stage neurofibrillary degeneration (Braak stage II) which, in the absence of neocortical amyloid-beta and neuritic plaques, was indicative of primary age-related tauopathy (PART). However, distinctive phospho-tau aggregates were observed subjacent to the subpial TTR amyloid deposits in all regions of the neocortex, including the primary motor and striate cortices, suggesting a potential link between TTR amyloid and neocortical tauopathy. Our report reveals novel insights into the potential neuropathologic substrates of dementia in variant TTR amyloidosis that need to be investigated in larger autopsy series. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40478-015-0216-0) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4496870 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44968702015-07-10 Neuropathologic analysis of Tyr69His TTR variant meningovascular amyloidosis with dementia Ziskin, Jennifer L. Greicius, Michael D. Zhu, Wan Okumu, Anna N. Adams, Christopher M. Plowey, Edward D. Acta Neuropathol Commun Case Report Transthyretin/TTR gene mutations usually cause systemic amyloidotic diseases. Few TTR variants preferentially affect the central nervous system, manifesting as oculoleptomeningeal amyloidosis. Patients with TTR meningovascular amyloidosis often show dementia, however the neuropathologic features of dementia in these cases have not been elucidated. We report the neuropathologic findings from a brain autopsy of a 72-year-old man with the rare Tyr69His (Y69H) TTR gene variant, dementia and ataxia. Severe amyloid deposits were observed in the leptomeninges and in a subpial and subependymal distribution. Mass spectrometry analysis demonstrated that the amyloid deposits were comprised of over 80 % of the variant TTR. TTR was undetectable by mass spectrometry in the neocortex subjacent to the subpial amyloid deposits. Subpial TTR amyloid deposits were associated with brisk superficial reactive gliosis and siderosis in the neocortex and cerebellar cortex. Subependymal TTR amyloid deposits were associated with subjacent myelin pallor in the hippocampal outflow tract structures including the alveus, fimbria and fornix. Phospho-tau immunostains demonstrated transentorhinal-stage neurofibrillary degeneration (Braak stage II) which, in the absence of neocortical amyloid-beta and neuritic plaques, was indicative of primary age-related tauopathy (PART). However, distinctive phospho-tau aggregates were observed subjacent to the subpial TTR amyloid deposits in all regions of the neocortex, including the primary motor and striate cortices, suggesting a potential link between TTR amyloid and neocortical tauopathy. Our report reveals novel insights into the potential neuropathologic substrates of dementia in variant TTR amyloidosis that need to be investigated in larger autopsy series. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40478-015-0216-0) contains supplementary material, which is available to authorized users. BioMed Central 2015-07-10 /pmc/articles/PMC4496870/ /pubmed/26156087 http://dx.doi.org/10.1186/s40478-015-0216-0 Text en © Ziskin et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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 | Case Report Ziskin, Jennifer L. Greicius, Michael D. Zhu, Wan Okumu, Anna N. Adams, Christopher M. Plowey, Edward D. Neuropathologic analysis of Tyr69His TTR variant meningovascular amyloidosis with dementia |
title | Neuropathologic analysis of Tyr69His TTR variant meningovascular amyloidosis with dementia |
title_full | Neuropathologic analysis of Tyr69His TTR variant meningovascular amyloidosis with dementia |
title_fullStr | Neuropathologic analysis of Tyr69His TTR variant meningovascular amyloidosis with dementia |
title_full_unstemmed | Neuropathologic analysis of Tyr69His TTR variant meningovascular amyloidosis with dementia |
title_short | Neuropathologic analysis of Tyr69His TTR variant meningovascular amyloidosis with dementia |
title_sort | neuropathologic analysis of tyr69his ttr variant meningovascular amyloidosis with dementia |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496870/ https://www.ncbi.nlm.nih.gov/pubmed/26156087 http://dx.doi.org/10.1186/s40478-015-0216-0 |
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