PMID- 19356689
OWN - NLM
STAT- MEDLINE
DCOM- 20090921
LR  - 20220309
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 159
IP  - 3
DP  - 2009 Mar 31
TI  - Vascular amyloid alters astrocytic water and potassium channels in mouse models 
      and humans with Alzheimer's disease.
PG  - 1055-69
LID - 10.1016/j.neuroscience.2009.01.023 [doi]
AB  - The neurovascular unit (NVU) comprises cerebral blood vessels and surrounding 
      astrocytes, neurons, perivascular microglia and pericytes. Astrocytes associated 
      with the NVU are responsible for maintaining cerebral blood flow and ionic and 
      osmotic balances in the brain. A significant proportion of individuals with 
      Alzheimer's disease (AD) have vascular amyloid deposits (cerebral amyloid 
      angiopathy, CAA) that contribute to the heterogeneous nature of the disease. To 
      determine whether NVU astrocytes are affected by the accumulation of amyloid at 
      cerebral blood vessels we examined astrocytic markers in four transgenic mouse 
      models of amyloid deposition. These mouse models represent mild CAA, moderate CAA 
      with disease progression to tau pathology and neuron loss, severe CAA and severe 
      CAA with disease progression to tau pathology and neuron loss. We found that CAA 
      and disease progression both resulted in distinct NVU astrocytic changes. CAA 
      causes a loss of apparent glial fibrillary acidic protein (GFAP)-positive 
      astrocytic end-feet and loss of water channels (aquaporin 4) localized to 
      astrocytic end feet. The potassium channels Kir4.1, an inward rectifying 
      potassium channel, and BK, a calcium-sensitive large-conductance potassium 
      channel, were also lost. The anchoring protein, dystrophin 1, is common to these 
      channels and was reduced in association with CAA. Disease progression was 
      associated with a phenotypic switch in astrocytes indicated by a loss of 
      GFAP-positive cells and a gain of S100 beta-positive cells. Aquaporin 4, Kir4.1 
      and dystrophin 1 were also reduced in autopsied brain tissue from individuals 
      with AD that also display moderate and severe CAA. Together, these data suggest 
      that damage to the neurovascular unit may be a factor in the pathogenesis of 
      Alzheimer's disease.
FAU - Wilcock, D M
AU  - Wilcock DM
AD  - Duke University Medical Center, Division of Neurology, Bryan Research Building, 
      Box 2900, Research Drive, Durham, NC 27710, USA. donna.wilcock@duke.edu
FAU - Vitek, M P
AU  - Vitek MP
FAU - Colton, C A
AU  - Colton CA
LA  - eng
GR  - R01 AG019740/AG/NIA NIH HHS/United States
GR  - AG19780/AG/NIA NIH HHS/United States
GR  - R01 AG019780/AG/NIA NIH HHS/United States
GR  - AG030942/AG/NIA NIH HHS/United States
GR  - R01 AG019780-05/AG/NIA NIH HHS/United States
GR  - P-30 AG028377/AG/NIA NIH HHS/United States
GR  - AG19740/AG/NIA NIH HHS/United States
GR  - F32 AG030942-02/AG/NIA NIH HHS/United States
GR  - F32 AG030942-01/AG/NIA NIH HHS/United States
GR  - R01 AG019740-05/AG/NIA NIH HHS/United States
GR  - F32 AG030942/AG/NIA NIH HHS/United States
GR  - P30 AG028377/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090119
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (AQP4 protein, human)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Aquaporin 4)
RN  - 0 (Dystrophin)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (KCNA6 protein, human)
RN  - 0 (Kcnj10 (channel))
RN  - 0 (Kv1.6 Potassium Channel)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Inwardly Rectifying)
RN  - 0 (Protease Nexins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Shaker Superfamily of Potassium Channels)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
SB  - IM
MH  - Aged, 80 and over
MH  - Alzheimer Disease/*physiopathology
MH  - Amyloid beta-Protein Precursor/genetics
MH  - Animals
MH  - Aquaporin 4/*metabolism
MH  - Astrocytes/pathology/*physiology
MH  - Brain/blood supply/physiopathology
MH  - Cerebral Amyloid Angiopathy/*physiopathology
MH  - Disease Models, Animal
MH  - Dystrophin/metabolism
MH  - Female
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Humans
MH  - Kv1.6 Potassium Channel
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Nitric Oxide Synthase Type II/genetics
MH  - Potassium Channels/*metabolism
MH  - Potassium Channels, Inwardly Rectifying/metabolism
MH  - Protease Nexins
MH  - RNA, Messenger
MH  - Receptors, Cell Surface/genetics
MH  - Shaker Superfamily of Potassium Channels/metabolism
PMC - PMC2699894
MID - NIHMS88850
EDAT- 2009/04/10 09:00
MHDA- 2009/09/22 06:00
PMCR- 2010/03/31
CRDT- 2009/04/10 09:00
PHST- 2008/09/30 00:00 [received]
PHST- 2009/01/13 00:00 [revised]
PHST- 2009/01/14 00:00 [accepted]
PHST- 2009/04/10 09:00 [entrez]
PHST- 2009/04/10 09:00 [pubmed]
PHST- 2009/09/22 06:00 [medline]
PHST- 2010/03/31 00:00 [pmc-release]
AID - S0306-4522(09)00043-8 [pii]
AID - 10.1016/j.neuroscience.2009.01.023 [doi]
PST - ppublish
SO  - Neuroscience. 2009 Mar 31;159(3):1055-69. doi: 
      10.1016/j.neuroscience.2009.01.023. Epub 2009 Jan 19.