PMID- 28755467
OWN - NLM
STAT- MEDLINE
DCOM- 20191107
LR  - 20200306
IS  - 1365-2990 (Electronic)
IS  - 0305-1846 (Print)
IS  - 0305-1846 (Linking)
VI  - 44
IP  - 5
DP  - 2018 Aug
TI  - Connexin-43 and aquaporin-4 are markers of ageing-related tau astrogliopathy 
      (ARTAG)-related astroglial response.
PG  - 491-505
LID - 10.1111/nan.12427 [doi]
AB  - AIMS: Ageing-related tau astrogliopathy (ARTAG) appears in subependymal, subpial, 
      perivascular, white matter (WM) and grey matter (GM) locations. Physical effects, 
      blood-brain barrier dysfunction and blood- or vessel-related factors have been 
      considered as aetiology. As connexin-43 (Cx43) and aquaporin-4 (AQP4) are related 
      to these, we hypothesized that their immunoreactivity (IR) varies with ARTAG in a 
      location-specific manner. METHODS: We performed a morphometric 
      immunohistochemical study measuring the densities of IR of Cx43, AQP4, AT8 
      (phospho-tau) and glial fibrillar acidic protein (GFAP). We analysed the amygdala 
      and hippocampus in age-matched cases with (n = 19) and without (n = 20) ARTAG in 
      each of the locations it aggregates. RESULTS: We show a dramatic increase 
      (>6-fold; P < 0.01) of Cx43 density of IR in ARTAG cases correlating strongly 
      with AT8 density of IR, irrespective of the presence of neuronal tau pathology or 
      reactive gliosis measured by GFAP density of IR, in the GM. In contrast, AQP4 
      density of IR was increased only in the WM and GM, and was associated with 
      increased AT8 density of IR only in WM and perivascular areas. DISCUSSION: Our 
      study reveals distinctive astroglial responses in each of the locations 
      associated with ARTAG. Our observations support the concept that factors related 
      to brain-fluid interfaces and water-ion imbalances most likely play a role in the 
      generation of ARTAG. As Cx43 is crucial for maintaining neuronal homeostasis, the 
      ARTAG-dependent increase of Cx43 density of IR suggests that the development of 
      ARTAG in the GM most likely indicates an early response to the degeneration of 
      neurons.
CI  - (c) 2017 British Neuropathological Society.
FAU - Kovacs, G G
AU  - Kovacs GG
AUID- ORCID: 0000-0003-3841-5511
AD  - Institute of Neurology, Medical University of Vienna, Vienna, Austria.
AD  - Center for Neurodegenerative Disease Research, Institute on Aging and Department 
      of Pathology and Laboratory Medicine of the Perelman School of Medicine at the 
      University of Pennsylvania, Philadelphia, PA, USA.
FAU - Yousef, A
AU  - Yousef A
AD  - Center for Neurodegenerative Disease Research, Institute on Aging and Department 
      of Pathology and Laboratory Medicine of the Perelman School of Medicine at the 
      University of Pennsylvania, Philadelphia, PA, USA.
FAU - Kaindl, S
AU  - Kaindl S
AD  - Institute of Neurology, Medical University of Vienna, Vienna, Austria.
FAU - Lee, V M
AU  - Lee VM
AD  - Center for Neurodegenerative Disease Research, Institute on Aging and Department 
      of Pathology and Laboratory Medicine of the Perelman School of Medicine at the 
      University of Pennsylvania, Philadelphia, PA, USA.
FAU - Trojanowski, J Q
AU  - Trojanowski JQ
AD  - Center for Neurodegenerative Disease Research, Institute on Aging and Department 
      of Pathology and Laboratory Medicine of the Perelman School of Medicine at the 
      University of Pennsylvania, Philadelphia, PA, USA.
LA  - eng
GR  - P30 AG010124/AG/NIA NIH HHS/United States
GR  - P30-AG10124/NH/NIH HHS/United States
GR  - P01 AG017586/AG/NIA NIH HHS/United States
GR  - NS088341/NH/NIH HHS/United States
GR  - R01 NS094003/NS/NINDS NIH HHS/United States
GR  - PO1-AG17586/NH/NIH HHS/United States
GR  - NS094003/NH/NIH HHS/United States
GR  - K23 NS088341/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20170825
PL  - England
TA  - Neuropathol Appl Neurobiol
JT  - Neuropathology and applied neurobiology
JID - 7609829
RN  - 0 (AQP4 protein, human)
RN  - 0 (Aquaporin 4)
RN  - 0 (Biomarkers)
RN  - 0 (Connexin 43)
RN  - 0 (GJA1 protein, human)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Aging/metabolism/*pathology
MH  - Aquaporin 4/analysis/*metabolism
MH  - Astrocytes/metabolism/*pathology
MH  - Biomarkers/analysis
MH  - Brain/metabolism/*pathology
MH  - Connexin 43/analysis/*metabolism
MH  - Female
MH  - Humans
MH  - Male
MH  - Tauopathies/metabolism/*pathology
PMC - PMC5788733
MID - NIHMS896112
OTO - NOTNLM
OT  - Tau
OT  - ageing-related tau astrogliopathy
OT  - aquaporin-4
OT  - blood-brain barrier
OT  - connexin 43
OT  - glial fibrillar acidic protein
COIS- Conflict of interest: The authors report no conflict of interest.
EDAT- 2017/07/30 06:00
MHDA- 2019/11/08 06:00
PMCR- 2019/08/01
CRDT- 2017/07/30 06:00
PHST- 2017/05/06 00:00 [received]
PHST- 2017/07/14 00:00 [revised]
PHST- 2017/07/24 00:00 [accepted]
PHST- 2017/07/30 06:00 [pubmed]
PHST- 2019/11/08 06:00 [medline]
PHST- 2017/07/30 06:00 [entrez]
PHST- 2019/08/01 00:00 [pmc-release]
AID - 10.1111/nan.12427 [doi]
PST - ppublish
SO  - Neuropathol Appl Neurobiol. 2018 Aug;44(5):491-505. doi: 10.1111/nan.12427. Epub 
      2017 Aug 25.