碩士 / 國立陽明大學 / 藥理學研究所 / 103 / Alzheimer’s disease (AD), the most common form of dementia, is a neurodegenerative disorder characterized by progressive impairment of cognitive function and behavior. Increasing evidence has showed that oxidative damage plays an important role in the pathogenesis of AD and several studies have demonstrated that lipid peroxidation is involved in the pathogenesis of AD. Acrolein (Acr), an α,β-unsaturated aldehyde, is an byproduct of lipid peroxidation and also ubiquitously exists in engine exhaust, tobacco and over-heated cooking oils and so on. It has been shown that Acr can be rapidly incorporated into proteins and generating a carbonyl derivatives to form protein-conjugated acrolein (PC-Acr) that can serve as a marker of oxidative damages. Previous studies have showed that PC-Acr or free form of Acr existed in brain tissues and plasma of AD patients, and that the urinary Acr metabolite, 3-hydroxypropyl mercapturic acid (3-HPMA), in AD subjects was higher than those in control subjects. However, it is still not known whether PC-Acr in plasma or 3-HPMA in urine come from brain tissues or not. In addition, there are no similar studies in Taiwan.
In order to develop early detection biomarkers for AD patients, this study collected and analyzed the levels of PC-Acr in CSF, plasma and urinary 3-HPMA in AD patients and control subjects from Taipei Veterans General Hospital in Taiwan. The results showed that the levels of PC-Acro in both CSF and plasma of AD patients were significantly higher than those of control subjects by immunnoblotting, and that the levels of urinary 3-HPMA of AD patients were higher than those of control subjects by LC-MS/MS. These results show that Acr produced from the brain of AD patients and then released to surrogate specimen such as CSF and plasma, and finally to urine. The data suggest that PC-Acr in CSF and plasma and the metabolite of Acr, 3-HPMA, in urine might serve as a surrogate marker for AD patients, and may help AD patients for early diagnosis in the future.
| Identifer | oai:union.ndltd.org:TW/103YM005550008 |
| Date | January 2015 |
| Creators | Wen-Chin Hsu, 許文菁 |
| Contributors | Tsung-Yun Liu, 劉宗榮 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 76 |
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