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.
Department of Pharmacology, Faculty of Science, Mahidol University, Phayathai, Bangkok, Thailand.
Nattinee
N
Jantaratnotai
Alden
A
Ling
Jenny
J
Cheng
Claudia
C
Schwab
Patrick L
PL
McGeer
James G
JG
McLarnon
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000503:physiopathology; D000704:Analysis of Variance; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid; D003863:Depression / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005470:Fluorometry; D057180:Frontotemporal Dementia / Q000134:cerebrospinal fluid; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000097:blood / Q000378:metabolism; D050784:Proto-Oncogene Protein c-ets-1 / Q000134:cerebrospinal fluid*; D015854:Up-Regulation / Q000502:physiology*; D016875:tau Proteins / Q000134:cerebrospinal fluid
D050784:Proto-Oncogene Protein c-ets-1; D016875:tau Proteins; D015260:Neprilysin