Hippocampal glutamate NMDA receptor loss tracks progression in Alzheimer's disease: quantitative autoradiography in postmortem human brain.
Early Alzheimer's disease (AD) is characterized by memory loss and hippocampal atrophy with relative sparing of basal ganglia. Activation of glutamate NMDA receptors in the hippocampus is an important step in memory formation. We measured the density of NMDA receptors in samples of hippocampus,...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3842934?pdf=render |
| _version_ | 1811230204584001536 |
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| author | Efrat Kravitz Inna Gaisler-Salomon Anat Biegon |
| author_facet | Efrat Kravitz Inna Gaisler-Salomon Anat Biegon |
| author_sort | Efrat Kravitz |
| collection | DOAJ |
| description | Early Alzheimer's disease (AD) is characterized by memory loss and hippocampal atrophy with relative sparing of basal ganglia. Activation of glutamate NMDA receptors in the hippocampus is an important step in memory formation. We measured the density of NMDA receptors in samples of hippocampus, entorhinal cortex and basal ganglia obtained from subjects who died with pathologically confirmed AD and age- and sex- matched non-demented controls. We found significant decreases in NMDA receptor density in the hippocampus and entorhinal cortex but not in the basal ganglia. Loss of NMDA receptors was significantly correlated with neuropathological progression as assessed by Braak staging postmortem. The same samples were probed for neuroinflammation by measuring the density and gene expression of translocator protein 18 kDA (TSPO), an established marker of microglial activation. Unlike NMDA receptor loss, increased densities of TSPO were found in all of the brain regions sampled. However hippocampal, but not striatal TSPO density and gene expression were inversely correlated with NMDA receptor density and positively correlated with Braak stage, suggesting NMDA receptors exacerbate neuroniflammatory damage. The high correlation between hippocampal NMDA receptor loss and disease progression supports the use of non invasive imaging with NMDA receptor tracers and positron emission tomography as a superior method for diagnosis, staging and treatment monitoring of AD in vivo. |
| first_indexed | 2024-04-12T10:24:57Z |
| format | Article |
| id | doaj.art-8e1c3329f9e64b10a5f1d59204bc0f8b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T10:24:57Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8e1c3329f9e64b10a5f1d59204bc0f8b2022-12-22T03:36:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01811e8124410.1371/journal.pone.0081244Hippocampal glutamate NMDA receptor loss tracks progression in Alzheimer's disease: quantitative autoradiography in postmortem human brain.Efrat KravitzInna Gaisler-SalomonAnat BiegonEarly Alzheimer's disease (AD) is characterized by memory loss and hippocampal atrophy with relative sparing of basal ganglia. Activation of glutamate NMDA receptors in the hippocampus is an important step in memory formation. We measured the density of NMDA receptors in samples of hippocampus, entorhinal cortex and basal ganglia obtained from subjects who died with pathologically confirmed AD and age- and sex- matched non-demented controls. We found significant decreases in NMDA receptor density in the hippocampus and entorhinal cortex but not in the basal ganglia. Loss of NMDA receptors was significantly correlated with neuropathological progression as assessed by Braak staging postmortem. The same samples were probed for neuroinflammation by measuring the density and gene expression of translocator protein 18 kDA (TSPO), an established marker of microglial activation. Unlike NMDA receptor loss, increased densities of TSPO were found in all of the brain regions sampled. However hippocampal, but not striatal TSPO density and gene expression were inversely correlated with NMDA receptor density and positively correlated with Braak stage, suggesting NMDA receptors exacerbate neuroniflammatory damage. The high correlation between hippocampal NMDA receptor loss and disease progression supports the use of non invasive imaging with NMDA receptor tracers and positron emission tomography as a superior method for diagnosis, staging and treatment monitoring of AD in vivo.http://europepmc.org/articles/PMC3842934?pdf=render |
| spellingShingle | Efrat Kravitz Inna Gaisler-Salomon Anat Biegon Hippocampal glutamate NMDA receptor loss tracks progression in Alzheimer's disease: quantitative autoradiography in postmortem human brain. PLoS ONE |
| title | Hippocampal glutamate NMDA receptor loss tracks progression in Alzheimer's disease: quantitative autoradiography in postmortem human brain. |
| title_full | Hippocampal glutamate NMDA receptor loss tracks progression in Alzheimer's disease: quantitative autoradiography in postmortem human brain. |
| title_fullStr | Hippocampal glutamate NMDA receptor loss tracks progression in Alzheimer's disease: quantitative autoradiography in postmortem human brain. |
| title_full_unstemmed | Hippocampal glutamate NMDA receptor loss tracks progression in Alzheimer's disease: quantitative autoradiography in postmortem human brain. |
| title_short | Hippocampal glutamate NMDA receptor loss tracks progression in Alzheimer's disease: quantitative autoradiography in postmortem human brain. |
| title_sort | hippocampal glutamate nmda receptor loss tracks progression in alzheimer s disease quantitative autoradiography in postmortem human brain |
| url | http://europepmc.org/articles/PMC3842934?pdf=render |
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