Upregulation and expression patterns of the angiogenic transcription factor ets-1 in Alzheimer's disease brain.


Immunohistochemical staining has been used to determine expression patterns of the angiogenic transcription factor, Ets-1, in the brains of Alzheimer's disease (AD) individuals. Brain tissue from non-demented controls showed little expression of Ets-1 whereas in AD brain tissue, Ets-1 was ubiquitously expressed in cortex and hippocampus. Double immunostaining with von Willerbrand factor demonstrated prominent Ets-1 intravascular immunoreactivity (ir) in AD cortical microvessels. In addition, Ets-1 also exhibited extravascular expression characterized by a diffuse pattern of Ets-1 ir in AD brain. Double staining also showed Ets-1 colocalization in microvasculature with the potent angiogenic agent, vascular endothelial growth factor (VEGF). Cell-associated tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine with pro-angiogenic activity, was primarily associated with diffuse extravascular Ets-1 ir. Clusters of HLA-DR positive microglia, resident immune cells of brain which release TNF-α, were also localized with diffuse Ets-1. Intravascular Ets-1 ir was maximally co-localized with soluble amyloid-β peptide (Aβ), Aβ1-40, in microvasculature whereas diffuse extravascular Ets-1 ir appeared in proximity to Aβ plaques in brain parenchyma. Similar overall results were obtained for patterns of Ets-1 staining in AD hippocampal tissue. This work provides novel findings on expression of the angiogenic transcription factor, Ets-1, in vascular remodeling and its association with pro-angiogenic factors, reactive microglia, and Aβ deposition in AD brain.

DOI: 10.3233/JAD-122191
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@article{Jantaratnotai2013UpregulationAE, title={Upregulation and expression patterns of the angiogenic transcription factor ets-1 in Alzheimer's disease brain.}, author={Nattinee Jantaratnotai and Alden Ling and Jenny M F Cheng and Claudia Schwab and Patrick L. Mcgeer and James G. McLarnon}, journal={Journal of Alzheimer's disease : JAD}, year={2013}, volume={37 2}, pages={367-77} }