Tags

Type your tag names separated by a space and hit enter

Vascular amyloid alters astrocytic water and potassium channels in mouse models and humans with Alzheimer's disease.
Neuroscience. 2009 Mar 31; 159(3):1055-69.N

Abstract

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.

Authors+Show Affiliations

Duke University Medical Center, Division of Neurology, Bryan Research Building, Box 2900, Research Drive, Durham, NC 27710, USA. donna.wilcock@duke.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19356689

Citation

Wilcock, D M., et al. "Vascular Amyloid Alters Astrocytic Water and Potassium Channels in Mouse Models and Humans With Alzheimer's Disease." Neuroscience, vol. 159, no. 3, 2009, pp. 1055-69.
Wilcock DM, Vitek MP, Colton CA. Vascular amyloid alters astrocytic water and potassium channels in mouse models and humans with Alzheimer's disease. Neuroscience. 2009;159(3):1055-69.
Wilcock, D. M., Vitek, M. P., & Colton, C. A. (2009). Vascular amyloid alters astrocytic water and potassium channels in mouse models and humans with Alzheimer's disease. Neuroscience, 159(3), 1055-69. https://doi.org/10.1016/j.neuroscience.2009.01.023
Wilcock DM, Vitek MP, Colton CA. Vascular Amyloid Alters Astrocytic Water and Potassium Channels in Mouse Models and Humans With Alzheimer's Disease. Neuroscience. 2009 Mar 31;159(3):1055-69. PubMed PMID: 19356689.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vascular amyloid alters astrocytic water and potassium channels in mouse models and humans with Alzheimer's disease. AU - Wilcock,D M, AU - Vitek,M P, AU - Colton,C A, Y1 - 2009/01/19/ PY - 2008/09/30/received PY - 2009/01/13/revised PY - 2009/01/14/accepted PY - 2009/4/10/entrez PY - 2009/4/10/pubmed PY - 2009/9/22/medline SP - 1055 EP - 69 JF - Neuroscience JO - Neuroscience VL - 159 IS - 3 N2 - 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. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/19356689/Vascular_amyloid_alters_astrocytic_water_and_potassium_channels_in_mouse_models_and_humans_with_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(09)00043-8 DB - PRIME DP - Unbound Medicine ER -