Down‐regulation of MET in hippocampal neurons of A lzheimer's disease brains
Abstract
We found that mRNA of MET, the receptor of hepatocyte growth factor (HGF), is significantly decreased in the hippocampus of Alzheimer's disease (AD) patients. Therefore, we tried to determine the cellular component-dependent changes of MET expressions. In this study, we examined cellular distribution of MET in the cerebral neocortices and hippocampi of 12 AD and 11 normal controls without brain diseases. In normal brains, MET immunoreactivity was observed in the neuronal perikarya and a subpopulation of astrocytes mainly in the subpial layer and white matter. In AD brains, we found marked decline of MET in hippocampal pyramidal neurons and granule cells of dentate gyrus. The decline was more obvious in the pyramidal neurons of the hippocampi than that in the neocortical neurons. In addition, we found strong MET immunostaining in reactive astrocytes, including those near senile plaques. Given the neurotrophic effects of the HGF/MET pathway, this decline may adversely affect neuronal survival in AD cases. Because it has been reported that HGF is also up-regulated around senile plaques, β-amyloid deposition might be associated with astrocytosis through the HGF signaling pathway.
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Clinical literature shows low levels of MET protein in the brains of AD patients and the MET gene as the most downregulated by transcriptome analysis.
“These findings are in keeping with clinical literature showing low levels of MET protein in the brains of AD patients and the MET gene as the most downregulated by transcriptome analysis [122,123].”
From Treatment of Alzheimer’s Disease: Beyond Symptomatic Therapies (2023) · cites this paper as [122]
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- Authors
- Hamasaki, H., Honda, H., Suzuki, S. O., Hokama, M., Kiyohara, Y., Nakabeppu, Y., & Iwaki, T.
- Affiliations
- Kyushu University (JP)
- Corresponding author
- Iwaki, Toru
- Venue
- Neuropathology
- Publisher
- Wiley
- Published
- 2014-01-21
- Volume
- 34
- Issue
- 3
- Pages
- 284-290
- ISSN
- 0919-6544 (ISSN-L)
- 1440-1789
- OpenAlex
- W2133852271
- Cited by
- 33
- References
- 32
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 7 · 2022: 2 · 2021: 5 · 2020: 2 · 2019: 4 · 2016: 2 · 2015: 1 · 2014: 1
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropathology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (22221004, 25430050)
- 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-Met, Alzheimer's disease, hippocampus, hepatocyte growth factor, pyramidal neurons, dentate gyrus granule cells, reactive astrocytes, amyloid plaques, amyloid-beta, astrocyte activation, neurotrophic signaling, neuronal survival
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Female, Hippocampus, Humans, Male, Middle Aged, Neurons, Biomarkers, Down-Regulation, Pyramidal Cells, Proto-Oncogene Proteins c-met
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