Dataset Information

Altered subcellular distribution of c-Abl in Alzheimer's disease.

ABSTRACT: c-Abl is a non-receptor tyrosine kinase that participates in multiple signaling pathways linking the cell surface, cytoskeleton, and the nucleus. Recent in vitro studies have also linked c-Abl to amyloid-beta-induced toxicity and tau phosphorylation. To further characterize a potential role of c-Abl in Alzheimer's disease (AD), we examined the expression and distribution of total and phosphorylated forms of c-Abl in the hippocampus of AD and control subjects. Laser scanning confocal microscopy was used to examine the colocalization of c-Abl with AD pathology. Our results demonstrate alterations in the presence and distribution of c-Abl and phosphorylated isoforms of c-Abl within the hippocampus during AD. Total unphosphorylated c-Abl was highest in non-demented control hippocampus. Activated isoforms of c-Abl were most abundant in AD hippocampus and co-localized with AD pathology, including granulovacuolar degeneration bodies, c-Abl interacts with phosphorylated tau in AD brain and may contribute to the formation of tau pathology. These studies demonstrate altered activation and distribution of c-Abl during AD, suggesting a role for c-Abl in Abeta signal transduction and generation of tau pathology in AD.

SUBMITTER: Jing Z

PROVIDER: S-EPMC2829466 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Altered subcellular distribution of c-Abl in Alzheimer's disease.

Jing Zheng Z Caltagarone John J Bowser Robert R

Journal of Alzheimer's disease : JAD 20090101 2

c-Abl is a non-receptor tyrosine kinase that participates in multiple signaling pathways linking the cell surface, cytoskeleton, and the nucleus. Recent in vitro studies have also linked c-Abl to amyloid-beta-induced toxicity and tau phosphorylation. To further characterize a potential role of c-Abl in Alzheimer's disease (AD), we examined the expression and distribution of total and phosphorylated forms of c-Abl in the hippocampus of AD and control subjects. Laser scanning confocal microscopy w ...[more]

PMID: 19363261

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Project description:Alzheimer's disease is the commonest form of dementia, but its cause still remains elusive. It is characterized by neurodegeneration, with amyloid-beta and tau aggregation. Recently, however, the roles of the vasculature and the neurovascular unit are being highlighted as important for disease progression. In particular, there is reduced microvascular density, and altered gene expression in vascular and glial cells. Structural changes naturally impact the functioning of the neurovascular unit, and the goal of the study was to quantify the corresponding changes in vivo, non-invasively. Our assessment is based on recordings of brain oxygenation, neuronal and cardiorespiratory activities, captured by functional near-infrared spectroscopy, electroencephalogram, electrocardiogram and respiration effort, respectively. Two groups were compared: an Alzheimer's disease group (N = 19) and a control group (N = 20) of similar age. The time-series were analysed using methods that can capture multi-scale and time-varying oscillations such as the wavelet transform power and wavelet phase coherence. The Alzheimer's disease group shows a significant decrease in the power of brain oxygenation oscillations compared to the control group. There is also a significant global reduction in the phase coherence between brain oxygenation time-series. The neurovascular phase coherence around 0.1 Hz is also significantly reduced in the Alzheimer's disease group. In addition, the average respiration rate is increased in the Alzheimer's disease group compared to the control group. We show that the phase coherence between vascular and neuronal activities is reduced in Alzheimer's disease compared to the control group, indicating altered functioning of the neurovascular unit. The brain oxygenation dynamics reveals reduced power and coordination of oscillations, especially in frequency ranges that are associated with vasomotion. This could lead to reduced oxygen delivery to the brain, which could affect ATP production, and potentially reduce amyloid-beta clearance. These changes in neurovascular dynamics have potential for early diagnosis, as a marker of disease progression, and for evaluating the effect of interventions.

Dataset Information

Altered subcellular distribution of c-Abl in Alzheimer's disease.

Publications

Altered subcellular distribution of c-Abl in Alzheimer's disease.

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