Down-regulation of MET in hippocampal neurons of Alzheimer's disease brains.
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.
Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Hideomi
H
Hamasaki
Hiroyuki
H
Honda
Satoshi O
SO
Suzuki
Masaaki
M
Hokama
Yutaka
Y
Kiyohara
Yusaku
Y
Nakabeppu
Toru
T
Iwaki
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D017966:Pyramidal Cells / Q000201:enzymology / Q000473:pathology
D015415:Biomarkers; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
Alzheimer's disease; HGF; MET; neurotrophic factor; senile plaque