Altered subcellular distribution of c-Abl in Alzheimer’s disease

Jing, Zheng; Caltagarone, John; Bowser, Robert

doi:10.3233/jad-2009-1062

Cited by 83Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Altered subcellular distribution of c-Abl in Alzheimer’s disease

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Jing, Zheng, Caltagarone, John, Bowser, Robert·2009·Journal of Alzheimer s Disease

DOI 10.3233/jad-2009-1062PMC PMC2829466

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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.

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c-Abl has been identified as an important pathogenic mediator of neurodegenerative diseases.
“Since c-Abl has been identified as an important pathogenic mediator of neurodegenerative diseases (Alvarez et al., 2004; Imam et al., 2011; Jing et al., 2009; Ko et al., 2010; Schlatterer et al., 2011)”
From Nilotinib restores memory function by preventing dopaminergic neuron degeneration in a mouse model of Alzheimer’s Disease (2021) · cites this paper as Jing et al., 2009
Phosphorylation of tyrosine residue 412 (p-c-Abl Y412) is important for c-Abl activation and colocalization with degenerating hippocampal neurons in AD subjects.
“Particularly, we examined the phosphorylation of tyrosine residue 412 (p-c-Abl Y412) that has been shown to be important for c-Abl activation and colocali zation with degenerating hippocampal neurons in AD subjects (Jing et al., 2009).”
From Nilotinib restores memory function by preventing dopaminergic neuron degeneration in a mouse model of Alzheimer’s Disease (2021) · cites this paper as Jing et al., 2009
The observation of an increase in c-Abl phosphorylation in Tg2576 mice is consistent with other studies that identify c-Abl as a pathogenesis mediator in AD.
“c-Abl is an important regulator of the autophagic process (Abushouk et al., 2018) and of other pathways that set the choice between survival and cell death, thus the observation of an increase in c-Abl phosphorylation in Tg2576 mice is consistent with other studies that identify c-Abl as a pathogenesis mediator in AD (Alvarez et al., 2004; Jing et al., 2009).”
From Nilotinib restores memory function by preventing dopaminergic neuron degeneration in a mouse model of Alzheimer’s Disease (2021) · cites this paper as Jing et al., 2009

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Authors: Jing, Z., Caltagarone, J., & Bowser, R.
Affiliations: Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA
University of Pittsburgh (US)
Corresponding author: Bowser, Robert
ORCID: Bowser, Robert
Venue: Journal of Alzheimer s Disease
Publisher: SAGE Publications
Published: 2009-06-05
Volume: 17
Issue: 2
Pages: 409-422
ISSN: 1387-2877 (ISSN-L)
1875-8908
DOI: 10.3233/jad-2009-1062
PMC: PMC2829466
OpenAlex: W1840896388
Cited by: 83
References: 38
Citations by year: 2026: 4 · 2025: 2 · 2024: 7 · 2023: 8 · 2022: 6 · 2021: 5 · 2020: 9 · 2019: 4 · 2018: 1 · 2017: 6 · 2016: 3 · 2015: 3 · 2014: 10 · 2013: 4 · 2012: 4
FWCI: 2.44
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Journal of Alzheimer s Disease (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute of Neurological Disorders and Stroke (NS042724, R01NS042724)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: c-Abl, Alzheimer's disease
MeSH terms: Aged, Aged, 80 and over, Alzheimer Disease, Amyloid, Analysis of Variance, Female, Hippocampus, Humans, Male, Middle Aged, Phosphorylation, Subcellular Fractions, Threonine, Tyrosine, Case-Control Studies, Proto-Oncogene Proteins c-abl, tau Proteins, Neurofilament Proteins, Microscopy, Confocal, Immunoprecipitation

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Altered subcellular distribution of c-Abl in Alzheimer’s disease

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