Characterization of the 18 kDa translocator protein (TSPO) expression in post‐mortem normal and Alzheimer's disease brains

The 18 kDa translocator protein (TSPO) is a widely used target for microglial PET imaging radioligands, but its expression in post‐mortem normal and diseased human brain is not well described. We aimed at characterizing the TSPO expression in human control (CTRL) and Alzheimer's disease (AD) br...

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Vydáno v:Brain pathology (Zurich, Switzerland) Ročník 30; číslo 1; s. 151 - 164
Hlavní autoři: Gui, Yaxing, Marks, Jordan D., Das, Sudeshna, Hyman, Bradley T., Serrano‐Pozo, Alberto
Médium: Journal Article
Jazyk:angličtina
Vydáno: Switzerland John Wiley & Sons, Inc 01.01.2020
John Wiley and Sons Inc
Témata:
18 kDa translocator protein (TSPO)
Alzheimer Disease - genetics
Alzheimer Disease - pathology
Alzheimer's disease
amyloid plaques
Astrocytes
Astrocytes - pathology
Autopsy - methods
Brain
Brain - pathology
Cerebral cortex
Disease control
Endothelial cells
Endothelial Cells - pathology
Gene Expression - genetics
Humans
Immunohistochemistry
Longitudinal Studies
Microglia
Microglia - pathology
mRNA
Muscles
Neocortex
Neurodegenerative diseases
Neurofibrillary tangles
Neurofibrillary Tangles - metabolism
Neuroglia - pathology
Neuroimaging
neuroinflammation
Neuronal-glial interactions
Neuropathology
peripheral benzodiazepine receptor
Plaque, Amyloid - pathology
Positron emission
Positron emission tomography
positron emission tomography (PET)
Proteins
Radioisotopes
Receptors, GABA - genetics
Receptors, GABA - metabolism
rs6971 SNP
Senile plaques
Smooth muscle
Substantia alba
Target recognition
Thickness
Tomography
Transcriptome - genetics
rs6971 SNP
neuroinflammation
positron emission tomography (PET)
neurofibrillary tangles
peripheral benzodiazepine receptor
18 kDa translocator protein (TSPO)
astrocytes
Alzheimer's disease
microglia
amyloid plaques
ISSN:1015-6305, 1750-3639, 1750-3639
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Shrnutí:The 18 kDa translocator protein (TSPO) is a widely used target for microglial PET imaging radioligands, but its expression in post‐mortem normal and diseased human brain is not well described. We aimed at characterizing the TSPO expression in human control (CTRL) and Alzheimer's disease (AD) brains. Specifically, we sought to: (1) define the cell type(s) expressing TSPO; (2) compare tspo mRNA and TSPO levels between AD and CTRL brains; (3) correlate TSPO levels with quantitative neuropathological measures of reactive glia and AD neuropathological changes; and (4) investigate the effects of the TSPO rs6971 SNP on tspo mRNA and TSPO levels, glial responses and AD neuropathological changes. We performed quantitative immunohistochemistry and Western blot in post‐mortem brain samples from CTRL and AD subjects, as well as analysis of publicly available mouse and human brain RNA‐Seq datasets. We found that: (1) TSPO is expressed not just in microglia, but also in astrocytes, endothelial cells and vascular smooth muscle cells; (2) there is substantial overlap of tspo mRNA and TSPO levels between AD and CTRL subjects and in TSPO levels between temporal neocortex and white matter in both groups; (3) TSPO cortical burden does not correlate with the burden of activated microglia or reactive astrocytes, Aβ plaques or neurofibrillary tangles, or the cortical thickness; (4) the TSPO rs6971 SNP does not significantly impact tspo mRNA or TSPO levels, the magnitude of glial responses, the cortical thickness, or the burden of AD neuropathological changes. These results could inform ongoing efforts toward the development of reactive glia‐specific PET radioligands.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:1015-6305
1750-3639
1750-3639
DOI:10.1111/bpa.12763