Selective Vulnerability of Brainstem Nuclei in Distinct Tauopathies: A Postmortem Study

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art_ESER_Selective_Vulnerability_of_Brainstem_Nuclei_in_Distinct_Tauopathies_2018.PDF (1.28 MB)
Citações na Scopus
37
Tipo de produção
article
Data de publicação
2018
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
OXFORD UNIV PRESS INC
Autores
ESER, Rana A.
EHRENBERG, Alexander J.
PETERSEN, Cathrine
DUNLOP, Sara
MEJIA, Maria B.
WALSH, Christine M.
RAJANA, Hima
OH, Jun
THEOFILAS, Panos
Citação
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, v.77, n.2, p.149-161, 2018
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
The brainstem nuclei of the reticular formation (RF) are critical for regulating homeostasis, behavior, and cognition. RF degenerates in tauopathies including Alzheimer disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). Although the burden of phopho-tau inclusion is high across these diseases, suggesting a similar vulnerability pattern, a distinct RF-associated clinical phenotype in these diseases indicates the opposite. To compare patterns of RF selective vulnerability to tauopathies, we analyzed 5 RF nuclei in tissue from 14 AD, 14 CBD, 10 PSP, and 3 control cases. Multidimensional quantitative analysis unraveled discernable differences on how these nuclei are vulnerable to AD, CBD, and PSP. For instance, PSP and CBD accrued more tau inclusions than AD in locus coeruleus, suggesting a lower vulnerability to AD. However, locus coeruleus neuronal loss in AD was so extreme that few neurons remained to develop aggregates. Likewise, tau burden in gigantocellular nucleus was low in AD and high in PSP, but few GABAergic neurons were present in AD. This challenges the hypothesis that gigantocellular nucleus neuronal loss underlies REM behavioral disorders because REM behavioral disorders rarely manifests in AD. This study provides foundation for characterizing the clinical consequences of RF degeneration in tauopathies and guiding customized treatment.
Palavras-chave
Alzheimer disease, Corticobasal degeneration, Human brainstem, Progressive supranuclear palsy, Reticular formation, Selective vulnerability, Tauopathies
URI
https://observatorio.fm.usp.br/handle/OPI/25502
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - LIM/22