Endothelin-converting enzyme-1 in Alzheimer's disease and vascular dementia

Research output: Contribution to journalArticle (Academic Journal)peer-review

27 Citations (Scopus)


AIMS: Alzheimer's disease (AD) is believed to be caused by the accumulation of amyloid beta (Aβ) peptide within the brain. Endothelin-converting enzyme-1 and 2 (ECE-1 and ECE-2) are expressed in endothelial cells and neurones, respectively, and both cleave 'big endothelin' to produce the vasoconstrictor endothelin-1 (ET-1). ECE-1 and ECE-2 also degrade Aβ. AD patients have regionally reduced microvascular blood flow in the brain, with impaired endothelium-dependent relaxation and cerebrovascular autoregulation, and abnormal production of ET-1 has been demonstrated in mice overexpressing amyloid precursor protein. We recently found ECE-2 mRNA and protein to be elevated in the brain in AD. In vitro, expression of ECE-2 was upregulated by Aβ. Our aims for this study were to examine expression of ECE-1 (which has 57% homology with ECE-2) in temporal cortex from patients with AD, vascular dementia (VaD) and controls. METHODS: We examined the distribution of ECE-1 with immunohistochemistry, and measured ECE-1 mRNA by real-time polymerase chain reaction (PCR). ECE-1 protein levels were measured by western blot, and results analysed before and after adjustment for factor VIII-related antigen. RESULTS: We showed ECE-1 to be in vascular endothelial cells. We did not find significant differences in ECE-1 mRNA or protein levels (either full-length ECE-1 or the soluble spliced variant, ECE-1sv) in AD or VaD compared with controls. CONCLUSIONS: Our findings suggest that any disease-specific contribution of ECE-1 to the accumulation of Aβ or reduction in local microvascular blood flow in AD or VaD is probably small, with abnormal production of ET-1 being more likely to reflect Aβ-mediated upregulation of ECE-2.
Translated title of the contributionEndothelin-converting enzyme-1 in Alzheimer's disease and vascular dementia
Original languageEnglish
Pages (from-to)487 - 497
Number of pages11
JournalNeuropathology and Applied Neurobiology
Volume36 (6)
Publication statusPublished - Oct 2010


Dive into the research topics of 'Endothelin-converting enzyme-1 in Alzheimer's disease and vascular dementia'. Together they form a unique fingerprint.

Cite this