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Language and spatial dysfunction in Alzheimer disease with white matter thorn-shaped astrocytes.
Resende, Elisa de Paula França; Nolan, Amber L; Petersen, Cathrine; Ehrenberg, Alexander J; Spina, Salvatore; Allen, Isabel E; Rosen, Howard J; Kramer, Joel; Miller, Bruce L; Seeley, William W; Gorno-Tempini, Maria Luiza; Miller, Zachary; Grinberg, Lea T.
Afiliación
  • Resende EPF; From the Memory and Aging Center (E.d.P.F.R., A.L.N., C.P., A.J.E., S.S., I.E.A., H.J.R., J.K., B.L.M., W.W.S., M.L.G.-T., Z.M., L.T.G.), Weill Institute for Neurosciences, and Department of Biostatistics and Epidemiology (L.T.G.), University of California, San Francisco; Global Brain Health Institu
  • Nolan AL; From the Memory and Aging Center (E.d.P.F.R., A.L.N., C.P., A.J.E., S.S., I.E.A., H.J.R., J.K., B.L.M., W.W.S., M.L.G.-T., Z.M., L.T.G.), Weill Institute for Neurosciences, and Department of Biostatistics and Epidemiology (L.T.G.), University of California, San Francisco; Global Brain Health Institu
  • Petersen C; From the Memory and Aging Center (E.d.P.F.R., A.L.N., C.P., A.J.E., S.S., I.E.A., H.J.R., J.K., B.L.M., W.W.S., M.L.G.-T., Z.M., L.T.G.), Weill Institute for Neurosciences, and Department of Biostatistics and Epidemiology (L.T.G.), University of California, San Francisco; Global Brain Health Institu
  • Ehrenberg AJ; From the Memory and Aging Center (E.d.P.F.R., A.L.N., C.P., A.J.E., S.S., I.E.A., H.J.R., J.K., B.L.M., W.W.S., M.L.G.-T., Z.M., L.T.G.), Weill Institute for Neurosciences, and Department of Biostatistics and Epidemiology (L.T.G.), University of California, San Francisco; Global Brain Health Institu
  • Spina S; From the Memory and Aging Center (E.d.P.F.R., A.L.N., C.P., A.J.E., S.S., I.E.A., H.J.R., J.K., B.L.M., W.W.S., M.L.G.-T., Z.M., L.T.G.), Weill Institute for Neurosciences, and Department of Biostatistics and Epidemiology (L.T.G.), University of California, San Francisco; Global Brain Health Institu
  • Allen IE; From the Memory and Aging Center (E.d.P.F.R., A.L.N., C.P., A.J.E., S.S., I.E.A., H.J.R., J.K., B.L.M., W.W.S., M.L.G.-T., Z.M., L.T.G.), Weill Institute for Neurosciences, and Department of Biostatistics and Epidemiology (L.T.G.), University of California, San Francisco; Global Brain Health Institu
  • Rosen HJ; From the Memory and Aging Center (E.d.P.F.R., A.L.N., C.P., A.J.E., S.S., I.E.A., H.J.R., J.K., B.L.M., W.W.S., M.L.G.-T., Z.M., L.T.G.), Weill Institute for Neurosciences, and Department of Biostatistics and Epidemiology (L.T.G.), University of California, San Francisco; Global Brain Health Institu
  • Kramer J; From the Memory and Aging Center (E.d.P.F.R., A.L.N., C.P., A.J.E., S.S., I.E.A., H.J.R., J.K., B.L.M., W.W.S., M.L.G.-T., Z.M., L.T.G.), Weill Institute for Neurosciences, and Department of Biostatistics and Epidemiology (L.T.G.), University of California, San Francisco; Global Brain Health Institu
  • Miller BL; From the Memory and Aging Center (E.d.P.F.R., A.L.N., C.P., A.J.E., S.S., I.E.A., H.J.R., J.K., B.L.M., W.W.S., M.L.G.-T., Z.M., L.T.G.), Weill Institute for Neurosciences, and Department of Biostatistics and Epidemiology (L.T.G.), University of California, San Francisco; Global Brain Health Institu
  • Seeley WW; From the Memory and Aging Center (E.d.P.F.R., A.L.N., C.P., A.J.E., S.S., I.E.A., H.J.R., J.K., B.L.M., W.W.S., M.L.G.-T., Z.M., L.T.G.), Weill Institute for Neurosciences, and Department of Biostatistics and Epidemiology (L.T.G.), University of California, San Francisco; Global Brain Health Institu
  • Gorno-Tempini ML; From the Memory and Aging Center (E.d.P.F.R., A.L.N., C.P., A.J.E., S.S., I.E.A., H.J.R., J.K., B.L.M., W.W.S., M.L.G.-T., Z.M., L.T.G.), Weill Institute for Neurosciences, and Department of Biostatistics and Epidemiology (L.T.G.), University of California, San Francisco; Global Brain Health Institu
  • Miller Z; From the Memory and Aging Center (E.d.P.F.R., A.L.N., C.P., A.J.E., S.S., I.E.A., H.J.R., J.K., B.L.M., W.W.S., M.L.G.-T., Z.M., L.T.G.), Weill Institute for Neurosciences, and Department of Biostatistics and Epidemiology (L.T.G.), University of California, San Francisco; Global Brain Health Institu
  • Grinberg LT; From the Memory and Aging Center (E.d.P.F.R., A.L.N., C.P., A.J.E., S.S., I.E.A., H.J.R., J.K., B.L.M., W.W.S., M.L.G.-T., Z.M., L.T.G.), Weill Institute for Neurosciences, and Department of Biostatistics and Epidemiology (L.T.G.), University of California, San Francisco; Global Brain Health Institu
Neurology ; 94(13): e1353-e1364, 2020 03 31.
Article en En | MEDLINE | ID: mdl-32001514
ABSTRACT

OBJECTIVES:

Alzheimer disease (AD) shows a broad array of clinical presentations, but the mechanisms underlying these phenotypic variants remain elusive. Aging-related astrogliopathy (ARTAG) is a relatively recent term encompassing a broad array of tau deposition in astroglia outside the range of traditional tauopathies. White matter thorn-shaped astrocyte (WM-TSA) clusters, a specific ARTAG subtype, has been associated with atypical language presentation of AD in a small study lacking replication. To interrogate the impact of WM-TSA in modifying clinical phenotype in AD, we investigated a clinicopathologic sample of 83 persons with pure cortical AD pathology and heterogeneous clinical presentations.

METHODS:

We mapped WM-TSA presence and density throughout cortical areas and interrogated whether WM-TSA correlated with atypical AD presentation or worse performance in neuropsychological testing.

RESULTS:

WM-TSA was present in nearly half of the cases and equally distributed in typical and atypical AD presentations. Worsening language and visuospatial functions were correlated with higher WM-TSA density in language-related and visuospatial-related regions, respectively. These findings were unrelated to regional neurofibrillary tangle burden. Next, unsupervised clustering divided the participants into 2 groups a high-WM-TSA (n = 9) and low-WM-TSA (n = 74) pathology signature. The high-WM-TSA group scored significantly worse in language but not in other cognitive domains.

CONCLUSIONS:

The negative impact of WM-TSA pathology to language and possibly visuospatial networks suggests that WM-TSA is not as benign as other ARTAG types and may be explored as a framework to understand the mechanisms and impact of astrocytic tau deposition in AD in humans.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Conducta Espacial / Astrocitos / Enfermedad de Alzheimer / Sustancia Blanca / Trastornos del Lenguaje Tipo de estudio: Observational_studies / Prevalence_studies / Risk_factors_studies Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Neurology Año: 2020 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Conducta Espacial / Astrocitos / Enfermedad de Alzheimer / Sustancia Blanca / Trastornos del Lenguaje Tipo de estudio: Observational_studies / Prevalence_studies / Risk_factors_studies Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Neurology Año: 2020 Tipo del documento: Article