Evaluating the Patterns of Aging-Related Tau Astrogliopathy Unravels Novel Insights Into Brain Aging and Neurodegenerative Diseases
Open accessAbstract
The term "aging-related tau astrogliopathy" (ARTAG) describes pathological accumulation of abnormally phosphorylated tau protein in astrocytes. We evaluated the correlates of ARTAG types (i.e., subpial, subependymal, white and gray matter, and perivascular) in different neuroanatomical regions. Clinical, neuropathological, and genetic (eg, APOE ε4 allele, MAPT H1/H2 haplotype) data from 628 postmortem brains from subjects were investigated; most of the patients had been longitudinally followed at the University of Pennsylvania. We found that (i) the amygdala is a hotspot for all ARTAG types; (ii) age at death, male sex, and presence of primary frontotemporal lobar degeneration (FTLD) tauopathy are significantly associated with ARTAG; (iii) age at death, greater degree of brain atrophy, ventricular enlargement, and Alzheimer disease (AD)-related variables are associated with subpial, white matter, and perivascular ARTAG types; (iv) AD-related variables are associated particularly with lobar white matter ARTAG; and (v) gray matter ARTAG in primary FTLD-tauopathies appears in areas without neuronal tau pathology. We provide a reference map of ARTAG types and propose at least 5 constellations of ARTAG. Furthermore, we propose a conceptual link between primary FTLD-tauopathy and ARTAG-related astrocytic tau pathologies. Our observations serve as a basis for etiological stratification and definition of progression patterns of ARTAG.
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ARTAG is often seen in individuals over the age of 60 who, despite accumulating p-tau, do not present with any clinical symptoms.
“ARTAG is often seen in individuals over the age of 60 who, despite accumulating p-tau, do not present with any clinical symptoms [80].”
From DNA repair deficiency and senescence in concussed professional athletes involved in contact sports (2019) · cites this paper as [80]
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- Authors
- Kovacs, G. G., Robinson, J. L., Xie, S. X., Lee, E. B., Grossman, M., Wolk, D. A., Irwin, D. J., Weintraub, D., Kim, C. F., Schuck, T., Yousef, A., Wagner, S. T., Suh, E., Van Deerlin, V. M., Lee, V. M.-Y., & Trojanowski, J. Q.
- Affiliations
- Medical University of Vienna (AT)
- Corresponding author
- Trojanowski, John Q.
- ORCID
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-03-14
- Volume
- 76
- Issue
- 4
- Pages
- 270-288
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- PMC
- PMC6251691
- OpenAlex
- W2606314986
- Cited by
- 132
- References
- 67
- Citations by year
- 2026: 14 · 2025: 11 · 2024: 9 · 2023: 13 · 2022: 13 · 2021: 15 · 2020: 15 · 2019: 18 · 2018: 17 · 2017: 7
- FWCI
- 11.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- National Institutes of Health (AG 10 124, AG 17586)
- National Institute on Aging (P30AG010124, P01AG017586)
- National Institute of Neurological Disorders and Stroke (K23NS088341, R01NS094003)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tau phosphorylation, astrocytes, brain aging, neurodegenerative diseases, amygdala, Alzheimer's disease, APOE ε4, brain atrophy, ventriculomegaly, neuropathology
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Apolipoproteins E, Astrocytes, Atrophy, Brain, Female, Humans, Longitudinal Studies, Male, Neuroglia, Sex Factors, tau Proteins, Neurodegenerative Diseases, Tauopathies, Frontotemporal Lobar Degeneration
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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