uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Loss of Astrocyte Polarization in the Tg-ArcSwe Mouse Model of Alzheimer's Disease
Show others and affiliations
2011 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, Vol. 27, no 4, 711-722 p.Article in journal (Refereed) Published
Abstract [en]

Aquaporin-4 (AQP4) is the predominant water channel in brain and is selectively expressed in astrocytes. Astrocytic endfoot membranes exhibit tenfold higher densities of AQP4 than non-endfoot membranes, making AQP4 an excellent marker of astrocyte polarization. Loss of astrocyte polarization is known to compromise astrocytic function and to be associated with impaired water and K+ homeostasis. Here we investigate by a combination of light and electron microscopic immunocytochemistry whether amyloid deposition is associated with a loss of astrocyte polarization, using AQP4 as a marker. We used the tg-ArcSwe mouse model of Alzheimer's disease, as this model displays perivascular plaques as well as plaques confined to the neuropil. 3D reconstructions were done to establish the spatial relation between plaques and astrocytic endfeet, the latter known to contain the perivascular pool of AQP4. Changes in AQP4 expression emerge just after the appearance of the first plaques. Typically, there is a loss of AQP4 from endfoot membranes at sites of perivascular amyloid deposits, combined with an upregulation of AQP4 in the neuropil surrounding plaques. By electron microscopy it could be verified that the upregulation reflects an increased concentration of AQP4 in those delicate astrocytic processes that abound in synaptic regions. Thus, astrocytes exhibit a redistribution of AQP4 from endfoot membranes to non-endfoot membrane domains. The present data suggest that the development of amyloid deposits is associated with a loss of astrocyte polarization. The possible perturbation of water and K+ homeostasis could contribute to cognitive decline and seizure propensity in patients with Alzheimer's disease.

Place, publisher, year, edition, pages
2011. Vol. 27, no 4, 711-722 p.
National Category
URN: urn:nbn:se:uu:diva-165011DOI: 10.3233/JAD-2011-110725ISI: 000298368100004PubMedID: 21891870OAI: oai:DiVA.org:uu-165011DiVA: diva2:471282
Available from: 2012-01-02 Created: 2012-01-02 Last updated: 2012-04-03Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Nilsson, Lars N GLannfelt, Lars
By organisation
In the same journal
Journal of Alzheimer's Disease

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 189 hits
ReferencesLink to record
Permanent link

Direct link