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

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorESER, Rana A.
dc.contributor.authorEHRENBERG, Alexander J.
dc.contributor.authorPETERSEN, Cathrine
dc.contributor.authorDUNLOP, Sara
dc.contributor.authorMEJIA, Maria B.
dc.contributor.authorSUEMOTO, Claudia K.
dc.contributor.authorWALSH, Christine M.
dc.contributor.authorRAJANA, Hima
dc.contributor.authorOH, Jun
dc.contributor.authorTHEOFILAS, Panos
dc.contributor.authorSEELEY, William W.
dc.contributor.authorMILLER, Bruce L.
dc.contributor.authorNEYLAN, Thomas C.
dc.contributor.authorHEINSEN, Helmut
dc.contributor.authorGRINBERG, Lea T.
dc.date.accessioned2018-03-06T15:15:02Z
dc.date.available2018-03-06T15:15:02Z
dc.date.issued2018
dc.description.abstractThe 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.
dc.description.indexMEDLINE
dc.description.sponsorshipTau Consortium/Rainwater charity foundation
dc.description.sponsorshipUC Berkeley's Undergraduate Research Apprentice Program
dc.description.sponsorship[P50AG023501]
dc.description.sponsorship[P01AG019724]
dc.description.sponsorship[K24AG053435]
dc.identifier.citationJOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, v.77, n.2, p.149-161, 2018
dc.identifier.doi10.1093/jnen/nlx113
dc.identifier.eissn1554-6578
dc.identifier.issn0022-3069
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/25502
dc.language.isoeng
dc.publisherOXFORD UNIV PRESS INC
dc.relation.ispartofJournal of Neuropathology and Experimental Neurology
dc.rightsrestrictedAccess
dc.rights.holderCopyright OXFORD UNIV PRESS INC
dc.subjectAlzheimer disease
dc.subjectCorticobasal degeneration
dc.subjectHuman brainstem
dc.subjectProgressive supranuclear palsy
dc.subjectReticular formation
dc.subjectSelective vulnerability
dc.subjectTauopathies
dc.subject.otherprogressive supranuclear palsy
dc.subject.otherpedunculopontine tegmental nucleus
dc.subject.otheralzheimers association guidelines
dc.subject.othersleep behavior disorder
dc.subject.otherdorsal raphe nucleus
dc.subject.othercorticobasal degeneration
dc.subject.otherlocus-coeruleus
dc.subject.otherneuropathologic assessment
dc.subject.othernational institute
dc.subject.othergabaergic neurons
dc.subject.wosClinical Neurology
dc.subject.wosNeurosciences
dc.subject.wosPathology
dc.titleSelective Vulnerability of Brainstem Nuclei in Distinct Tauopathies: A Postmortem Study
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryisous
hcfmusp.author.externalESER, Rana A.:Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA
hcfmusp.author.externalEHRENBERG, Alexander J.:Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA
hcfmusp.author.externalPETERSEN, Cathrine:Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA
hcfmusp.author.externalDUNLOP, Sara:Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA
hcfmusp.author.externalMEJIA, Maria B.:Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA
hcfmusp.author.externalWALSH, Christine M.:Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA
hcfmusp.author.externalRAJANA, Hima:Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA
hcfmusp.author.externalOH, Jun:Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA
hcfmusp.author.externalTHEOFILAS, Panos:Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA
hcfmusp.author.externalSEELEY, William W.:Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA; Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA
hcfmusp.author.externalMILLER, Bruce L.:Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA
hcfmusp.author.externalNEYLAN, Thomas C.:Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA; Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA; Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA
hcfmusp.citation.scopus37
hcfmusp.contributor.author-fmusphcCLAUDIA KIMIE SUEMOTO
hcfmusp.contributor.author-fmusphcHELMUT MANFRED HEINSEN
hcfmusp.contributor.author-fmusphcLEA TENENHOLZ GRINBERG
hcfmusp.description.beginpage149
hcfmusp.description.endpage161
hcfmusp.description.issue2
hcfmusp.description.volume77
hcfmusp.origemWOS
hcfmusp.origem.pubmed29304218
hcfmusp.origem.scopus2-s2.0-85041506573
hcfmusp.origem.wosWOS:000424149600006
hcfmusp.publisher.cityCARY
hcfmusp.publisher.countryUSA
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