Heme oxygenase-1 is a 32 kDa protein that catalyzes the degradation of heme to biliverdin in brain and other tissues. Our laboratory had previously reported significantly decreased HO-1 protein levels in AD plasma and CSF and HO-1 mRNA in AD mononuclear cells (which may be chemically unstable relative to the levels seen in normal elderly control (NEC) subjects). We hypothesized that there exists a heme oxygenase-1 suppressor (HOS) factor in the plasma of AD patients. Using a novel, glial-based bioassay, we showed that plasma HOS activity was detected in 23/24 AD patients, 3/8 mild cognitive impairment (MCI) patients and in 0/21 NEC patients (HOS activity signifying HO-1 suppression of >50% compared to positive controls). Antioxidant exposure and hypercortisolemia did not account for the HOS activity in AD plasma. We investigated the specificity and selectivity of the HOS factor by analyzing plasma derived from patients with non-Alzheimer's dementia's and non-dementing neurological disorders. We conclude that a HOS factor exists in the plasma of sporadic AD and some MCI patients but is undetectable in NEC plasma. The presence of a circulating HOS factor may further signify systemic redox derangements in early sporadic AD and provide a possible biological marker for this condition.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.80306 |
| Date | January 2004 |
| Creators | Kravitz, Steven |
| Contributors | Schipper, Hyman M. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Division of Neuroscience.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002031530, proquestno: AAIMQ98675, Theses scanned by UMI/ProQuest. |
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