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Pathologic correlates of aging-related tau astrogliopathy: ARTAG is associated with LATE-NC and cerebrovascular pathologies, but not with ADNC.
Katsumata, Yuriko; Wu, Xian; Aung, Khine Zin; Gauthreaux, Kathryn; Mock, Charles; Forrest, Shelley L; Kovacs, Gabor G; Nelson, Peter T.
Afiliação
  • Katsumata Y; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506, United States of America; Department of Biostatistics, University of Kentucky, Lexington, KY 40506, United States of America.
  • Wu X; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506, United States of America; Department of Biostatistics, University of Kentucky, Lexington, KY 40506, United States of America.
  • Aung KZ; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506, United States of America; Department of Biostatistics, University of Kentucky, Lexington, KY 40506, United States of America.
  • Gauthreaux K; National Alzheimer's Coordinating Center, Department of Epidemiology, University of Washington, Seattle, WA 98105, United States of America.
  • Mock C; National Alzheimer's Coordinating Center, Department of Epidemiology, University of Washington, Seattle, WA 98105, United States of America.
  • Forrest SL; Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Canada; Laboratory Medicine Program and Krembil Brain Institute, University Health Network, Toronto, Canada.
  • Kovacs GG; Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Canada; Laboratory Medicine Program and Krembil Brain Institute, University Health Network, Toronto, Canada.
  • Nelson PT; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506, United States of America; Department of Pathology, Division of Neuropathology, University of Kentucky, Lexington, KY, United States of America. Electronic address: pnels2@email.uky.edu.
Neurobiol Dis ; 191: 106412, 2024 Feb.
Article em En | MEDLINE | ID: mdl-38244935
ABSTRACT
Age-related tau astrogliopathy (ARTAG) is detectable in the brains of over one-third of autopsied persons beyond age 80, but the pathoetiology of ARTAG is poorly understood. Insights can be gained by analyzing risk factors and comorbid pathologies. Here we addressed the question of which prevalent co-pathologies are observed with increased frequency in brains with ARTAG. The study sample was the National Alzheimer's Coordinating Center (NACC) data set, derived from multiple Alzheimer's disease research centers (ADRCs) in the United States. Data from persons with unusual conditions (e.g. frontotemporal dementia) were excluded leaving 504 individual autopsied research participants, clustering from 20 different ADRCs, autopsied since 2020; ARTAG was reported in 222 (44.0%) of included participants. As has been shown previously, ARTAG was increasingly frequent with older age and in males. The presence and severity of other common subtypes of pathology that were previously linked to dementia were analyzed, stratifying for the presence of ARTAG. In logistical regression-based statistical models that included age and sex as covariates, ARTAG was relatively more likely to be found in brains with limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and in brains with comorbid cerebrovascular pathology (arteriolosclerosis and/or brain infarcts). However, ARTAG was not associated with severe Alzheimer's disease neuropathologic change (ADNC), or primary age-related tauopathy (PART). In a subset analysis of 167 participants with neurocognitive testing data, there was a marginal trend for ARTAG pathology to be associated with cognitive impairment as assessed with MMSE scores (P = 0.07, adjusting for age, sex, interval between final clinic visit and death, and ADNC severity). A limitation of the study was that there were missing data about ARTAG pathologies, with incomplete operationalization of ARTAG according to anatomic region and pathologic subtypes (e.g., thorn-shaped or granular-fuzzy astrocytes). In summary, ARTAG was not associated with ADNC, whereas prior observations about ARTAG occurring with increased frequency in aging, males, and brains with LATE-NC were replicated. It remains to be determined whether the increased frequency of ARTAG in brains with comorbid cerebrovascular pathology is related to local infarctions or neuroinflammatory signaling, or with some other set of correlated factors including blood-brain barrier dysfunction.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Demência / Proteinopatias TDP-43 / Doença de Alzheimer Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Aged80 / Humans / Male Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Demência / Proteinopatias TDP-43 / Doença de Alzheimer Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Aged80 / Humans / Male Idioma: En Ano de publicação: 2024 Tipo de documento: Article