PMID- 31947996
OWN - NLM
STAT- MEDLINE
DCOM- 20200602
LR  - 20220129
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 1
DP  - 2020 Jan 4
TI  - NDRG2 Expression Correlates with Neurofibrillary Tangles and Microglial Pathology 
      in the Ageing Brain.
LID - 10.3390/ijms21010340 [doi]
LID - 340
AB  - Astrocytes play a major role in the pathogenesis of a range of neurodegenerative 
      diseases, including Alzheimer's disease (AD), undergoing dramatic morphological 
      and molecular changes that can cause potentially both beneficial and detrimental 
      effects. They comprise a heterogeneous population, requiring a panel of specific 
      phenotype markers to identify astrocyte subtypes, changes in function and their 
      relation to pathology. This study aimed to characterise expression of the 
      astrocyte marker N-myc downstream regulated gene 2 (NDRG2) in the ageing brain, 
      investigate the relationship between NDRG2 and a panel of astrocyte markers, and 
      relate NDRG2 expression to pathology. NDRG2 specifically immunolabelled the cell 
      body and radiating processes of astrocytes in the temporal cortex of the 
      Cognitive Function and Ageing Study (CFAS) neuropathology cohort. Expression of 
      NDRG2 did not correlate with other astrocyte markers, including glial fibrillary 
      acidic protein (GFAP), excitatory amino acid transporter 2 (EAAT2) and glutamine 
      synthetase (GS). NDRG2 showed a relationship to AT8(+) neurofibrillary tangles (p 
      = 0.001) and CD68(+) microglia (p = 0.047), but not beta-amyloid plaques or 
      astrocyte nuclear gammaH2AX immunoreactivity, a marker of DNA damage response. These 
      findings provide new insight into the astrocyte response to pathology in the 
      ageing brain, and suggest NDRG2 may be a potential target to modulate this 
      response.
FAU - Fadul, Motaz M
AU  - Fadul MM
AUID- ORCID: 0000-0002-2208-9988
AD  - Department of Neuroscience, Sheffield Institute for Translational Neuroscience, 
      University of Sheffield, Sheffield S10 2HQ, UK.
FAU - Garwood, Claire J
AU  - Garwood CJ
AD  - Department of Neuroscience, Sheffield Institute for Translational Neuroscience, 
      University of Sheffield, Sheffield S10 2HQ, UK.
FAU - Waller, Rachel
AU  - Waller R
AUID- ORCID: 0000-0001-5815-8829
AD  - Department of Neuroscience, Sheffield Institute for Translational Neuroscience, 
      University of Sheffield, Sheffield S10 2HQ, UK.
FAU - Garrett, Navonna
AU  - Garrett N
AD  - Department of Neuroscience, Sheffield Institute for Translational Neuroscience, 
      University of Sheffield, Sheffield S10 2HQ, UK.
FAU - Heath, Paul R
AU  - Heath PR
AUID- ORCID: 0000-0002-8385-1438
AD  - Department of Neuroscience, Sheffield Institute for Translational Neuroscience, 
      University of Sheffield, Sheffield S10 2HQ, UK.
FAU - Matthews, Fiona E
AU  - Matthews FE
AUID- ORCID: 0000-0002-1728-2388
AD  - Population Health Sciences Institute, University of Newcastle, Newcastle NE4 5PL, 
      UK.
FAU - Brayne, Carol
AU  - Brayne C
AUID- ORCID: 0000-0001-5307-663X
AD  - Department of Public Health and Primary Care, Institute of Public Health, 
      University of Cambridge, Cambridge CB2 0SR, UK.
FAU - Wharton, Stephen B
AU  - Wharton SB
AUID- ORCID: 0000-0003-2785-333X
AD  - Department of Neuroscience, Sheffield Institute for Translational Neuroscience, 
      University of Sheffield, Sheffield S10 2HQ, UK.
FAU - Simpson, Julie E
AU  - Simpson JE
AUID- ORCID: 0000-0002-3753-4271
AD  - Department of Neuroscience, Sheffield Institute for Translational Neuroscience, 
      University of Sheffield, Sheffield S10 2HQ, UK.
LA  - eng
GR  - -/King Abdulaziz University/
GR  - G0601022/MRC_/Medical Research Council/United Kingdom
GR  - G0900582/MRC_/Medical Research Council/United Kingdom
GR  - G9901400/MRC_/Medical Research Council/United Kingdom
GR  - G0300126/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20200104
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (CD68 antigen, human)
RN  - 0 (Excitatory Amino Acid Transporter 2)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (NDRG2 protein, human)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (tau Proteins)
RN  - EC 6.3.1.2 (Glutamate-Ammonia Ligase)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - *Aging
MH  - Alzheimer Disease/metabolism/*pathology
MH  - Antigens, CD/metabolism
MH  - Antigens, Differentiation, Myelomonocytic/metabolism
MH  - Astrocytes/cytology/metabolism
MH  - Brain/*metabolism/pathology
MH  - DNA Damage
MH  - Excitatory Amino Acid Transporter 2/metabolism
MH  - Gene Expression Regulation
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Glutamate-Ammonia Ligase/metabolism
MH  - Humans
MH  - Microglia/*metabolism/pathology
MH  - Neurofibrillary Tangles/*metabolism
MH  - Tumor Suppressor Proteins/genetics/*metabolism
MH  - tau Proteins/metabolism
PMC - PMC6982267
OTO - NOTNLM
OT  - N-myc downstream regulated gene 2 (NDRG2)
OT  - ageing brain
OT  - astrocyte
OT  - neurofibrillary tangles
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2020/01/18 06:00
MHDA- 2020/06/03 06:00
PMCR- 2020/01/01
CRDT- 2020/01/18 06:00
PHST- 2019/12/12 00:00 [received]
PHST- 2020/01/02 00:00 [accepted]
PHST- 2020/01/18 06:00 [entrez]
PHST- 2020/01/18 06:00 [pubmed]
PHST- 2020/06/03 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - ijms21010340 [pii]
AID - ijms-21-00340 [pii]
AID - 10.3390/ijms21010340 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Jan 4;21(1):340. doi: 10.3390/ijms21010340.