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Close association of water channel AQP1 with amyloid-beta deposition in Alzheimer disease brains.

ABSTRACT: Aquaporin-1 (AQP1), a membrane water channel protein, is expressed exclusively in the choroid plexus epithelium in the central nervous system under physiological conditions. However, AQP1 expression is enhanced in reactive astrocytes, accumulating in brain lesions of Creutzfeldt-Jakob disease and multiple sclerosis, suggesting a role of AQP1-expressing astrocytes in brain water homeostasis under pathological conditions. To clarify a pathological implication of AQP1 in Alzheimer disease (AD), we investigated the possible relationship between amyloid-beta (Abeta) deposition and astrocytic AQP1 expression in the motor cortex and hippocampus of 11 AD patients and 16 age-matched other neurological disease cases. In all cases, AQP1 was expressed exclusively in a subpopulation of multipolar fibrillary astrocytes. The great majority of AQP1-expressing astrocytes were located either on the top of or in close proximity to Abeta plaques in AD brains but not in non-AD cases, whereas those independent of Abeta deposition were found predominantly in non-AD brains. By Western blot, cultured human astrocytes constitutively expressed AQP1, and the levels of AQP1 protein expression were not affected by exposure to Abeta(1-42) peptide, but were elevated by hypertonic sodium chloride. By immunoprecipitation, the C-terminal fragment-beta (CTFbeta) of amyloid precursor protein interacted with the N-terminal half of AQP1 spanning the transmembrane helices H1, H2 and H3. These observations suggest the possible association of astrocytic AQP1 with Abeta deposition in AD brains.

SUBMITTER: Misawa T

PROVIDER: S-EPMC2516196 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Close association of water channel AQP1 with amyloid-beta deposition in Alzheimer disease brains.

Misawa Tamako T Arima Kunimasa K Mizusawa Hidehiro H Satoh Jun-ichi J

Acta neuropathologica 20080529 3

Aquaporin-1 (AQP1), a membrane water channel protein, is expressed exclusively in the choroid plexus epithelium in the central nervous system under physiological conditions. However, AQP1 expression is enhanced in reactive astrocytes, accumulating in brain lesions of Creutzfeldt-Jakob disease and multiple sclerosis, suggesting a role of AQP1-expressing astrocytes in brain water homeostasis under pathological conditions. To clarify a pathological implication of AQP1 in Alzheimer disease (AD), we ...[more]

PMID: 18509662

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Project description:BackgroundThe role of viral infection in Alzheimer Disease (AD) pathogenesis is an area of great interest in recent years. Several studies have suggested an association between the human roseoloviruses, HHV-6 and HHV-7, and AD. Amyloid-β (Aβ) plaques are a hallmark neuropathological finding of AD and were recently proposed to have an antimicrobial function in response to infection. Identifying a causative and mechanistic role of human roseoloviruses in AD has been confounded by limitations in performing in vivo studies. Recent -omics based approaches have demonstrated conflicting associations between human roseoloviruses and AD. Murine roseolovirus (MRV) is a natural murine pathogen that is highly-related to the human roseoloviruses, providing an opportunity to perform well-controlled studies of the impact of roseolovirus on Aβ deposition.MethodsWe utilized the 5XFAD mouse model to test whether MRV induces Aβ deposition in vivo. We also evaluated viral load and neuropathogenesis of MRV infection. To evaluate Aβ interaction with MRV, we performed electron microscopy. RNA-sequencing of a cohort of AD brains compared to control was used to investigate the association between human roseolovirus and AD.ResultsWe found that 5XFAD mice were susceptible to MRV infection and developed neuroinflammation. Moreover, we demonstrated that Aβ interacts with viral particles in vitro and, subsequent to this interaction, can disrupt infection. Despite this, neither peripheral nor brain infection with MRV increased or accelerated Aβ plaque formation. Moreover, -omics based approaches have demonstrated conflicting associations between human roseoloviruses and AD. Our RNA-sequencing analysis of a cohort of AD brains compared to controls did not show an association between roseolovirus infection and AD.ConclusionAlthough MRV does infect the brain and cause transient neuroinflammation, our data do not support a role for murine or human roseoloviruses in the development of Aβ plaque formation and AD.

Dataset Information

Close association of water channel AQP1 with amyloid-beta deposition in Alzheimer disease brains.

Publications

Close association of water channel AQP1 with amyloid-beta deposition in Alzheimer disease brains.

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