PMID- 36331509
OWN - NLM
STAT- MEDLINE
DCOM- 20230103
LR  - 20230119
IS  - 1554-6578 (Electronic)
IS  - 0022-3069 (Linking)
VI  - 82
IP  - 1
DP  - 2022 Dec 19
TI  - Silence of resident microglia in GPI anchorless prion disease and activation of 
      microglia in Gerstmann-Straussler-Scheinker disease and sporadic 
      Creutzfeldt-Jakob disease.
PG  - 38-48
LID - 10.1093/jnen/nlac098 [doi]
AB  - GPI anchorless prion diseases (GPIALPs) show numerous coarse prion protein (PrP) 
      deposits in the CNS but neuropil spongiform changes are mild and the incidence of 
      dementia is low. Here, we examined differences in resident microglial phenotypes 
      between GPIALP (D178fs25) and the other prion diseases 
      Gerstmann-Straussler-Scheinker (GSS) disease and sporadic Creutzfeldt-Jakob 
      disease (sCJD) with respect to homeostasis and activation. Immunohistochemistry 
      was performed on 2 GPIALP (D178fs25), 4 GSS (P102L), and 4 sCJD cases. 
      Homeostatic microglia expressing TMEM119 and P2RY12 were preserved in GPIALP 
      compared to GSS and sCJD. Microglia/macrophage activation in GSS and sCJD was 
      associated with the extent of spongiform change. Immunoelectron microscopy 
      revealed TMEM119 and P2RY12 in PrP plaque cores. Activated microglia/macrophages 
      expressing HLA-DR and CD68 were predominant in GSS and sCJD whereas in GPIALP, 
      homeostatic microglia were retained and activated microglia/macrophages were 
      rarely observed. These data suggest that PrP deposition in GPIALP is less toxic 
      and that microglia may be immune-tolerant to PrP deposition. This may be 
      associated with milder tissue damage and a low incidence of dementia. Whereas 
      microglia/macrophage activation is considered to be a reaction to tissue injury, 
      this study shows that the degree of microglia/macrophage activity might influence 
      the extent of tissue damage.
CI  - (c) The Author(s) 2022. Published by Oxford University Press on behalf of American 
      Association of Neuropathologists, Inc. All rights reserved. For permissions, 
      please email: journals.permissions@oup.com.
FAU - Noguchi, Hideko
AU  - Noguchi H
AD  - Department of Neuropathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Koyama, Sachiko
AU  - Koyama S
AD  - Department of Neuropathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Yagita, Kaoru
AU  - Yagita K
AD  - Department of Neuropathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Shijo, Masahiro
AU  - Shijo M
AD  - Department of Neuropathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Matsuzono, Kosuke
AU  - Matsuzono K
AD  - Division of Neurology, Department of Medicine, Jichi Medical University, Tochigi, 
      Japan.
FAU - Hamasaki, Hideomi
AU  - Hamasaki H
AD  - Department of Neuropathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Kanemaru, Takaaki
AU  - Kanemaru T
AD  - Department of Morphology Core Unit, Kyushu University Hospital, Fukuoka, Japan.
FAU - Okamoto, Tsuyoshi
AU  - Okamoto T
AD  - Faculty of Arts and Science, Kyushu University, Fukuoka, Japan.
FAU - Kai, Keita
AU  - Kai K
AD  - Department of Pathology, Saga University Hospital, Saga, Japan.
FAU - Aishima, Shinichi
AU  - Aishima S
AD  - Department of Pathology and Microbiology, Faculty of Medicine, Saga University, 
      Saga, Japan.
FAU - Abe, Koji
AU  - Abe K
AD  - National Center of Neurology and Psychiatry, Tokyo, Japan.
FAU - Sasagasako, Naokazu
AU  - Sasagasako N
AD  - Department of Neurology, Neuro Muscular Center, National Hospital Organization 
      Omuta National Hospital, Fukuoka, Japan.
FAU - Honda, Hiroyuki
AU  - Honda H
AUID- ORCID: 0000-0002-4225-7248
AD  - Department of Neuropathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (Prion Proteins)
RN  - 0 (Tmem119 protein, human)
RN  - 0 (P2RY12 protein, human)
RN  - 0 (Receptors, Purinergic P2Y12)
RN  - 0 (Membrane Proteins)
RN  - Creutzfeldt-Jakob Disease, Sporadic
SB  - IM
MH  - Humans
MH  - *Creutzfeldt-Jakob Syndrome/metabolism
MH  - *Gerstmann-Straussler-Scheinker Disease/genetics
MH  - *Microglia/metabolism
MH  - Prion Proteins/genetics/metabolism
MH  - *Receptors, Purinergic P2Y12/genetics/metabolism
MH  - *Membrane Proteins/genetics/metabolism
OTO - NOTNLM
OT  - GPI anchorless
OT  - Homeostatic microglia
OT  - Prion
OT  - Prion protein plaque
OT  - Resident microglia
EDAT- 2022/11/05 06:00
MHDA- 2022/12/22 06:00
CRDT- 2022/11/04 11:34
PHST- 2022/11/05 06:00 [pubmed]
PHST- 2022/12/22 06:00 [medline]
PHST- 2022/11/04 11:34 [entrez]
AID - 6798824 [pii]
AID - 10.1093/jnen/nlac098 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2022 Dec 19;82(1):38-48. doi: 10.1093/jnen/nlac098.