Accumulation of tumor-suppressor PTEN in Alzheimer neurofibrillary tangles
Open accessAbstract
The phosphatase and tensin homologue deleted on chromosome 10 (PTEN) negatively regulates intracellular levels of PIP3 and antagonizes the PI3K signaling pathway important for cell survival. The present study determined whether altered distribution of PTEN occurs in Alzheimer's disease (AD) brains. We investigated a possible role for PTEN in postmortem brain tissues from elderly controls and patients with AD using immunoblotting and microscopic analyses. Intense immunolabeling was found in the large neurons such as pyramidal cells. In normal neurons, PTEN was located in the nucleus, the cytoplasm of cell bodies and the proximal portion of apical dendrites. Reduced expression and redistribution of PTEN was seen in the remaining neurons in AD. In addition, PTEN was redistributed in damaged neurons from the nucleus and cytoplasm to neuritic pathology such as intracellular neurofibrillary tangles (NFTs), neuropil threads and dystrophic neurites within senile plaques in AD hippocampus, subiculum, entorhinal cortex and angular gyrus. Furthermore, double immunofluorescence staining showed dual labeling of intracellular NFTs for PTEN and tau, labeling of some axons for PTEN and phosphorylated neurofilament, and weak labeling of a few reactive astrocytes around senile plaques for PTEN and GFAP. Double labeling of NFTs was observed in a subset of tangle-bearing neurons either for PTEN and GSK3beta or for PTEN and MEK. Thus our results suggest that PTEN delocalized from the nucleus to the cytoplasm and to intracellular NFTs may cause a deregulation of PI3K pathway in the cytoplasm and may induce the nuclear dysfunction of PTEN in AD degenerating neurons.
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Nuclear and cytoplasmic PTEN staining is decreased in brains of Alzheimer's patients compared to normal aging.
“Sonoda et al. [31] observed a decrease in nuclear and cytoplasmic staining in brains of Alzheimer’s patients compared to brains of individuals with normal aging.”
From Repair of Oxidative DNA Damage, Cell-Cycle Regulation and Neuronal Death May Influence the Clinical Manifestation of Alzheimer’s Disease (2014) · cites this paper as [31]
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- Authors
- Sonoda, Y., Mukai, H., Matsuo, K., Takahashi, M., Ono, Y., Maeda, K., Akiyama, H., & Kawamata, T.
- Affiliations
- Kobe University (JP)
- Biosignal Research Center, Kobe University (JP)
- Tokyo Institute of Psychiatry (JP)
- Corresponding author
- Kawamata, Toshio
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 471
- Issue
- 1
- Pages
- 20-24
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W2085245632
- Cited by
- 74
- References
- 26
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 6 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 6 · 2017: 3 · 2016: 10 · 2015: 5 · 2014: 5 · 2013: 3 · 2012: 5
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Kobe University Repository Kernel (Kobe University) (submittedVersion, other-oa)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (20591024)
- 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
- PTEN, Alzheimer's disease, neurofibrillary tangles, PI3K signaling, phosphatidylinositol 3,4,5-trisphosphate, tau protein, GSK3β, MEK, amyloid plaques, neurodegeneration, hippocampus, subiculum, entorhinal cortex, angular gyrus, neurofilament phosphorylation, astrocytes
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Astrocytes, Female, Glial Fibrillary Acidic Protein, Humans, Male, Middle Aged, Neurons, Phosphorylation, Neurofibrillary Tangles, tau Proteins, Phosphatidylinositol 3-Kinases, Protein Transport, PTEN Phosphohydrolase
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