TY - JOUR
T1 - Factors associated with development and distribution of granular/fuzzy astrocytes in neurodegenerative diseases
AU - Miki, Tomoko
AU - Yokota, Osamu
AU - Haraguchi, Takashi
AU - Ishizu, Hideki
AU - Hasegawa, Masato
AU - Ishihara, Takeshi
AU - Ueno, Shu ichi
AU - Takenoshita, Shintaro
AU - Terada, Seishi
AU - Yamada, Norihito
N1 - Funding Information:
We thank Mses. Y. Matsuo and M. Onbe for their technical assistance. This work was supported by Grants-in-Aid for Scientific Research (C) from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT KAKENHI Grant No. 18K07559), Grants-in-Aid from the Research Committee of CNS Degenerative Diseases and Research on Dementia from the Ministry of Health, Labor and Welfare of Japan (H29-Nanchi-Ippan-033), an Intramural Research Grant for Neurological and Psychiatric Disorders from National Center of Neurology and Psychiatry (NCNP) (30-8), grants from the Strategic Research Program for Brain Sciences from Japan Agency for Medical Research and Development (AMED, JP20dm0107109) and grants from Zikei Institute of Psychiatry.
Funding Information:
We thank Mses. Y. Matsuo and M. Onbe for their technical assistance. This work was supported by Grants‐in‐Aid for Scientific Research (C) from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT KAKENHI Grant No. 18K07559), Grants‐in‐Aid from the Research Committee of CNS Degenerative Diseases and Research on Dementia from the Ministry of Health, Labor and Welfare of Japan (H29‐Nanchi‐Ippan‐033), an Intramural Research Grant for Neurological and Psychiatric Disorders from National Center of Neurology and Psychiatry (NCNP) (30‐8), grants from the Strategic Research Program for Brain Sciences from Japan Agency for Medical Research and Development (AMED, JP20dm0107109) and grants from Zikei Institute of Psychiatry.
Publisher Copyright:
© 2020 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Granular/fuzzy astrocytes (GFAs), a subtype of “aging-related tau astrogliopathy,” are noted in cases bearing various neurodegenerative diseases. However, the pathogenic significance of GFAs remains unclear. We immunohistochemically examined the frontal cortex, caudate nucleus, putamen and amygdala in 105 cases composed of argyrophilic grain disease cases (AGD, N = 26), and progressive supranuclear palsy (PSP, N = 10), Alzheimer’s disease (AD, N = 20) and primary age-related tauopathy cases (PART, N = 18) lacking AGD, as well as 31 cases bearing other various neurodegenerative diseases to clarify (i) the distribution patterns of GFAs in AGD, and PSP, AD and PART lacking AGD, (ii) the impacts of major pathological factors and age on GFA formation and (iii) immunohistochemical features useful to understand the formation process of GFAs. In AGD cases, GFAs consistently occurred in the amygdala (100%), followed by the putamen (69.2%) and caudate nucleus and frontal cortex (57.7%, respectively). In PSP cases without AGD, GFAs were almost consistently noted in all regions examined (90–100%). In AD cases without AGD, GFAs were less frequent, developing preferably in the putamen (35.0%) and caudate nucleus (30.0%). PART cases without AGD had GFAs most frequently in the amygdala (35.3%), being more similar to AGD than to AD cases. Ordered logistic regression analyses using all cases demonstrated that the strongest independent factor of GFA formation in the frontal cortex and striatum was the diagnosis of PSP, while that in the amygdala was AGD. The age was not significantly associated with GFA formation in any region. In GFAs in AGD cases, phosphorylation and conformational change of tau, Gallyas-positive glial threads indistinguishable from those in tufted astrocytes, and the activation of autophagy occurred sequentially. Given these findings, AGD, PSP, AD and PART cases may show distinct distributions of GFAs, which may provide clues to predict the underlying processes of primary tauopathies.
AB - Granular/fuzzy astrocytes (GFAs), a subtype of “aging-related tau astrogliopathy,” are noted in cases bearing various neurodegenerative diseases. However, the pathogenic significance of GFAs remains unclear. We immunohistochemically examined the frontal cortex, caudate nucleus, putamen and amygdala in 105 cases composed of argyrophilic grain disease cases (AGD, N = 26), and progressive supranuclear palsy (PSP, N = 10), Alzheimer’s disease (AD, N = 20) and primary age-related tauopathy cases (PART, N = 18) lacking AGD, as well as 31 cases bearing other various neurodegenerative diseases to clarify (i) the distribution patterns of GFAs in AGD, and PSP, AD and PART lacking AGD, (ii) the impacts of major pathological factors and age on GFA formation and (iii) immunohistochemical features useful to understand the formation process of GFAs. In AGD cases, GFAs consistently occurred in the amygdala (100%), followed by the putamen (69.2%) and caudate nucleus and frontal cortex (57.7%, respectively). In PSP cases without AGD, GFAs were almost consistently noted in all regions examined (90–100%). In AD cases without AGD, GFAs were less frequent, developing preferably in the putamen (35.0%) and caudate nucleus (30.0%). PART cases without AGD had GFAs most frequently in the amygdala (35.3%), being more similar to AGD than to AD cases. Ordered logistic regression analyses using all cases demonstrated that the strongest independent factor of GFA formation in the frontal cortex and striatum was the diagnosis of PSP, while that in the amygdala was AGD. The age was not significantly associated with GFA formation in any region. In GFAs in AGD cases, phosphorylation and conformational change of tau, Gallyas-positive glial threads indistinguishable from those in tufted astrocytes, and the activation of autophagy occurred sequentially. Given these findings, AGD, PSP, AD and PART cases may show distinct distributions of GFAs, which may provide clues to predict the underlying processes of primary tauopathies.
KW - aging-related tau astrogliopathy
KW - argyrophilic grain
KW - granular/fuzzy astrocyte
KW - primary age-related tauopathy
KW - tau
KW - tufted astrocyte
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U2 - 10.1111/bpa.12843
DO - 10.1111/bpa.12843
M3 - Article
C2 - 32293067
AN - SCOPUS:85085095849
SN - 1015-6305
VL - 30
SP - 811
EP - 830
JO - Brain Pathology
JF - Brain Pathology
IS - 4
ER -