ArticleNeurology2020
Language and spatial dysfunction in Alzheimer disease with white matter thorn-shaped astrocytes.
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Article in Neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
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18 citing papers in PubMed, 34 citations in OpenAlex.
- Medial temporal ageing-related tau astrogliopathy below 66 years is associated with neurodegeneration.Brain : a journal of neurology · 2026Article
- Traumatic brain injury or head impacts from contact sports are associated with tau astrogliopathy.Brain : a journal of neurology · 2025Article
- Grey matter ageing-related tau astrogliopathy: associations with brain pathologies and cognitive decline.Brain : a journal of neurology · 2024Article
- Pathologic correlates of aging-related tau astrogliopathy: ARTAG is associated with LATE-NC and cerebrovascular pathologies, but not with ADNC.Neurobiology of disease · 2024Article
- Exploring the Role of Machine Learning in Diagnosing and Treating Speech Disorders: A Systematic Literature Review.Psychology research and behavior management · 2024Review
- Alzheimer's disease heterogeneity explained by polygenic risk scores derived from brain transcriptomic profiles.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Elevated serum platelet count inhibits the effects of brain functional changes on cognitive function in patients with mild cognitive impairment: A resting-state functional magnetic resonance imaging study.Frontiers in aging neuroscience · 2023Article
- DHCR24 Knockdown Induces Tau Hyperphosphorylation at Thr181, Ser199, Ser262, and Ser396 Sites via Activation of the Lipid Raft-Dependent Ras/MEK/ERK Signaling Pathway in C8D1A Astrocytes.Molecular neurobiology · 2022Article
- Relationships among tau burden, atrophy, age, and naming in the aphasic variant of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Article
- Comorbid neuropathological diagnoses in early versus late-onset Alzheimer's disease.Brain : a journal of neurology · 2021Article
- Aging-Related Tau Astrogliopathy in Aging and Neurodegeneration.Brain sciences · 2021Review
- Space-occupying brain lesions, trauma-related tau astrogliopathy, and ARTAG: a report of two cases and a literature review.Acta neuropathologica communications · 2021Review
- New insights into atypical Alzheimer's disease in the era of biomarkers.The Lancet. Neurology · 2021Review
- Multiple system aging-related tau astrogliopathy with complex proteinopathy in an oligosymptomatic octogenarian.Neuropathology : official journal of the Japanese Society of Neuropathology · 2021Article
- Cerebral Microbleeds, Cerebrospinal Fluid, and Neuroimaging Markers in Clinical Subtypes of Alzheimer's Disease.Frontiers in neurology · 2021Article
- Astroglia and Tau: New Perspectives.Frontiers in aging neuroscience · 2020Review
- Comorbid neuropathology and atypical presentation of Alzheimer's disease.Alzheimer's & dementia (Amsterdam, Netherlands)Article
- FTLD-TDP versus LATE-NC: Experience of a Brain Bank specializing in FTLD-TDP.Alzheimer's & dementia (Amsterdam, Netherlands)Article
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Authors and funding
13 authors at 1 institution in 3 countries.
Elisa de Paula França ResendeFrom 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 Institute based at University of California (E.d.P.F.R., L.T.G.), San Francisco; Trinity College (E.d.P.F.R., L.T.G.), Dublin, Ireland; Department of Neurology (E.d.P.F.R.), Federal University of Minas Gerais, Belo Horizonte, Brazil; Department of Integrative Biology (A.J.E.), University of California, Berkeley; and Department of Pathology (L.T.G.), Lim-22, Lim-66, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Amber L NolanFrom 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 Institute based at University of California (E.d.P.F.R., L.T.G.), San Francisco; Trinity College (E.d.P.F.R., L.T.G.), Dublin, Ireland; Department of Neurology (E.d.P.F.R.), Federal University of Minas Gerais, Belo Horizonte, Brazil; Department of Integrative Biology (A.J.E.), University of California, Berkeley; and Department of Pathology (L.T.G.), Lim-22, Lim-66, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Cathrine PetersenFrom 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 Institute based at University of California (E.d.P.F.R., L.T.G.), San Francisco; Trinity College (E.d.P.F.R., L.T.G.), Dublin, Ireland; Department of Neurology (E.d.P.F.R.), Federal University of Minas Gerais, Belo Horizonte, Brazil; Department of Integrative Biology (A.J.E.), University of California, Berkeley; and Department of Pathology (L.T.G.), Lim-22, Lim-66, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Alexander J EhrenbergFrom 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 Institute based at University of California (E.d.P.F.R., L.T.G.), San Francisco; Trinity College (E.d.P.F.R., L.T.G.), Dublin, Ireland; Department of Neurology (E.d.P.F.R.), Federal University of Minas Gerais, Belo Horizonte, Brazil; Department of Integrative Biology (A.J.E.), University of California, Berkeley; and Department of Pathology (L.T.G.), Lim-22, Lim-66, University of Sao Paulo Medical School, Sao Paulo, Brazil.ORCID 0000-0003-4334-9424
Salvatore SpinaFrom 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 Institute based at University of California (E.d.P.F.R., L.T.G.), San Francisco; Trinity College (E.d.P.F.R., L.T.G.), Dublin, Ireland; Department of Neurology (E.d.P.F.R.), Federal University of Minas Gerais, Belo Horizonte, Brazil; Department of Integrative Biology (A.J.E.), University of California, Berkeley; and Department of Pathology (L.T.G.), Lim-22, Lim-66, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Isabel E AllenFrom 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 Institute based at University of California (E.d.P.F.R., L.T.G.), San Francisco; Trinity College (E.d.P.F.R., L.T.G.), Dublin, Ireland; Department of Neurology (E.d.P.F.R.), Federal University of Minas Gerais, Belo Horizonte, Brazil; Department of Integrative Biology (A.J.E.), University of California, Berkeley; and Department of Pathology (L.T.G.), Lim-22, Lim-66, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Howard J RosenFrom 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 Institute based at University of California (E.d.P.F.R., L.T.G.), San Francisco; Trinity College (E.d.P.F.R., L.T.G.), Dublin, Ireland; Department of Neurology (E.d.P.F.R.), Federal University of Minas Gerais, Belo Horizonte, Brazil; Department of Integrative Biology (A.J.E.), University of California, Berkeley; and Department of Pathology (L.T.G.), Lim-22, Lim-66, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Joel KramerFrom 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 Institute based at University of California (E.d.P.F.R., L.T.G.), San Francisco; Trinity College (E.d.P.F.R., L.T.G.), Dublin, Ireland; Department of Neurology (E.d.P.F.R.), Federal University of Minas Gerais, Belo Horizonte, Brazil; Department of Integrative Biology (A.J.E.), University of California, Berkeley; and Department of Pathology (L.T.G.), Lim-22, Lim-66, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Bruce L MillerFrom 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 Institute based at University of California (E.d.P.F.R., L.T.G.), San Francisco; Trinity College (E.d.P.F.R., L.T.G.), Dublin, Ireland; Department of Neurology (E.d.P.F.R.), Federal University of Minas Gerais, Belo Horizonte, Brazil; Department of Integrative Biology (A.J.E.), University of California, Berkeley; and Department of Pathology (L.T.G.), Lim-22, Lim-66, University of Sao Paulo Medical School, Sao Paulo, Brazil.
William W SeeleyFrom 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 Institute based at University of California (E.d.P.F.R., L.T.G.), San Francisco; Trinity College (E.d.P.F.R., L.T.G.), Dublin, Ireland; Department of Neurology (E.d.P.F.R.), Federal University of Minas Gerais, Belo Horizonte, Brazil; Department of Integrative Biology (A.J.E.), University of California, Berkeley; and Department of Pathology (L.T.G.), Lim-22, Lim-66, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Maria Luiza Gorno-TempiniFrom 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 Institute based at University of California (E.d.P.F.R., L.T.G.), San Francisco; Trinity College (E.d.P.F.R., L.T.G.), Dublin, Ireland; Department of Neurology (E.d.P.F.R.), Federal University of Minas Gerais, Belo Horizonte, Brazil; Department of Integrative Biology (A.J.E.), University of California, Berkeley; and Department of Pathology (L.T.G.), Lim-22, Lim-66, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Zachary MillerFrom 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 Institute based at University of California (E.d.P.F.R., L.T.G.), San Francisco; Trinity College (E.d.P.F.R., L.T.G.), Dublin, Ireland; Department of Neurology (E.d.P.F.R.), Federal University of Minas Gerais, Belo Horizonte, Brazil; Department of Integrative Biology (A.J.E.), University of California, Berkeley; and Department of Pathology (L.T.G.), Lim-22, Lim-66, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Lea T GrinbergFrom 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 Institute based at University of California (E.d.P.F.R., L.T.G.), San Francisco; Trinity College (E.d.P.F.R., L.T.G.), Dublin, Ireland; Department of Neurology (E.d.P.F.R.), Federal University of Minas Gerais, Belo Horizonte, Brazil; Department of Integrative Biology (A.J.E.), University of California, Berkeley; and Department of Pathology (L.T.G.), Lim-22, Lim-66, University of Sao Paulo Medical School, Sao Paulo, Brazil. lea.grinberg@ucsf.edu.
Universidade Federal de Minas Gerais · BR
Funding
TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2MVIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BREWER, JAMES B · 1985 to 2018
$55.4MResearch Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Serggio Carlo Lanata · 2019 to 2026
$36.9MPrPSc SPECIFIC INTERACTION WITH NOVEL PrP-Fc FUSION PROTEINSP50AG023501 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MILLER, BRUCE L · 2004 to 2018
$27.1MProgressive Aphasia Cognition Anatomy and ProgressionR01NS050915 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARIA LUISA GORNO TEMPINI · 2004 to 2026
$11.0MDynamic Brain Imaging of Speech in Primary Progressive AphasiaR01NS100440 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARIA LUISA GORNO TEMPINI, John Francis Houde · 2017 to 2026
$3.6MTraining program in the neurology of language and neurodegenerative aphasiasK24DC015544 · NIDCD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GORNO TEMPINI, MARIA LUISA · 2016 to 2025
$1.9MNeuropathological changes underlying clinical heterogeneity in Alzheimer diseaseK24AG053435 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRINBERG, LEA TENENHOLZ · 2016 to 2025
$1.8MNeuropathological basis of brain network dysfunctionK08AG052648 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SPINA, SALVATORE · 2016 to 2020
$852kNIA NIH HHS K08 AG052648NIA NIH HHS K24 AG053435NIA NIH HHS P01 AG019724NIA NIH HHS P30 AG062422NIA NIH HHS P50 AG005131NIA NIH HHS P50 AG023501NIDCD NIH HHS K24 DC015544NINDS NIH HHS R01 NS050915NINDS NIH HHS R01 NS100440
Abstract
objectivesAlzheimer 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.
methodsWe 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.
resultsWM-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.
conclusionsThe 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.
Indexed as
AgedAged, 80 and overAlzheimer DiseaseAstrocytesBrainCross-Sectional StudiesFemaleHumansLanguage DisordersMaleMiddle AgedPhenotypeSpatial BehaviorWhite Matter
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