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

Abstract

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.

• Authors: Nattinee Jantaratnotai, Alden Ling, Jenny Cheng, Claudia Schwab, Patrick L McGeer, James G McLarnon
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 37 Issue 2 Pg. 367-77 ( 2013) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 23948889 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Proto-Oncogene Protein c-ets-1
• tau Proteins
• Neprilysin

Topics

• Age Factors
• Aged
• Aged, 80 and over
• Alzheimer Disease (cerebrospinal fluid, physiopathology)
• Analysis of Variance
• Creutzfeldt-Jakob Syndrome (cerebrospinal fluid)
• Depression (cerebrospinal fluid)
• Enzyme-Linked Immunosorbent Assay
• Female
• Fluorometry
• Frontotemporal Dementia (cerebrospinal fluid)
• Humans
• Linear Models
• Male
• Middle Aged
• Neprilysin (blood, metabolism)
• Proto-Oncogene Protein c-ets-1 (cerebrospinal fluid)
• Up-Regulation (physiology)
• tau Proteins (cerebrospinal fluid)