Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 19, Issue 2, Pages 673-679Publisher
IOS PRESS
DOI: 10.3233/JAD-2010-1265
Keywords
Alzheimer's disease; amyloid-beta protein precursor processing; LRRTM3; neuron; pre-eclampsia; STOX1; trophoblast
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Funding
- SAFE [LSHB-CT-2004-503243]
- Foundation for Translational Research (STR)
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Pre-eclampsia and late-onset Alzheimer's disease (LOAD) share no clinical features. In contrast to these clinical dissimilarities, striking parallels exist between the (epi)genetic features associated with pre-eclampsia and LOAD for the genes located on 10q22. The parallels in identity between the 10q22 genes involved and active in the organs (placenta, brain) primarily affected in the respective diseases led us to explore, if the pre-eclampsia susceptibility gene STOX1 is functionally involved in LOAD. We demonstrate that isoform A of STOX1 is abundantly expressed in the brain, correlates with severity of disease, and selectively transactivates LRRTM3 in neural cells with increased amyloid-beta protein precursor processing. Similar in vitro results were seen in trophoblast. Our data indicate that STOX1 controls a conserved pathway shared between placenta and brain with overexpression in LOAD.
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