Evaluating the Patterns of Aging-Related Tau Astrogliopathy Unravels Novel Insights Into Brain Aging and Neurodegenerative Diseases.
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.
Institute of Neurology, Medical University of Vienna, Vienna, Austria.|Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology & Laboratory Medicine, Philadelphia, PA, USA.
Gabor G
GG
Kovacs
Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology & Laboratory Medicine, Philadelphia, PA, USA.
John L
JL
Robinson
Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Sharon X
SX
Xie
Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology & Laboratory Medicine, Philadelphia, PA, USA.
Edward B
EB
Lee
Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Murray
M
Grossman
Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
David A
DA
Wolk
Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
David J
DJ
Irwin
Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Dan
D
Weintraub
Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology & Laboratory Medicine, Philadelphia, PA, USA.
Christopher F
CF
Kim
Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology & Laboratory Medicine, Philadelphia, PA, USA.
Theresa
T
Schuck
Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology & Laboratory Medicine, Philadelphia, PA, USA.
Ahmed
A
Yousef
Institute of Neurology, Medical University of Vienna, Vienna, Austria.
Stephanie T
ST
Wagner
Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology & Laboratory Medicine, Philadelphia, PA, USA.
Eunran
E
Suh
Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology & Laboratory Medicine, Philadelphia, PA, USA.
Vivianna M
VM
Van Deerlin
Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology & Laboratory Medicine, Philadelphia, PA, USA.
Virginia M-Y
VM
Lee
Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology & Laboratory Medicine, Philadelphia, PA, USA.
John Q
JQ
Trojanowski
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000473:pathology; D001057:Apolipoproteins E / Q000096:biosynthesis / Q000235:genetics; D001253:Astrocytes / Q000473:pathology*; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics / Q000473:pathology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D019636:Neurodegenerative Diseases / Q000473:pathology*; D009457:Neuroglia / Q000473:pathology*; D012737:Sex Factors; D024801:Tauopathies / Q000473:pathology*; D016875:tau Proteins / Q000096:biosynthesis / Q000235:genetics
D001057:Apolipoproteins E; C054369:MAPT protein, human; D016875:tau Proteins
ARTAG; Aging-related tau astrogliopathy; Alzheimer disease; Chronic traumatic encephalopathy; Dementia; Tau; Tauopathy