알츠하이머병 환자에서 산화적 스트레스에 대한 요산의 보상적 역할
Uric Acid as a Compensator for Oxidative Stress in Alzheimer’s Disease
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Background: Uric acid (UA) is known to have neuroprotective effects by acting as a major plasma antioxidant. However, it is also known to be a pro-oxidant under certain circumstances. In this study, we analysed the association between UA and homocystein, which is a well-known pro-oxidant, as well as the association between UA and cognitive function in order to evaluate the neuroprotective function of UA in neurodegenerative disease progression. Methods: Plasma UA and homocystein, along with the two other major plasma antioxidants albumin and bilirubin, were measured in 133 Alzhiemer’s disease (AD) patients, 98 Mild cognitive impairment (MCI) patients, and 77 normal elderly controls. The cognitive function of the subjects was evaluated by Mini Mental Status Examination (MMSE). By using linear regression analysis, we investigated the association between UA with homocystein in each of these groups. Furthermore, the association between UA levels and the MMSE score was also analyzed. All analyses were adjusted for age, sex, education, hypertension, and diabetes mellitus. Results: Homocystein increased in MCI, AD group compared with the control group. In the AD group, there was a statistically significant increase of UA compared with the MCI group, after adjusting for age, gender, hypertension, diabetes mellitus, and education (p=0.017). Linear regression analysis showed that increasing homocystein predicted increasing UA in MCI and AD patients (β=1.12, SE=0.36, p=0.002; β=1.79, SE=0.43, p<0.001, respectively). Furthermore, increasing UA predicted increasing MMSE in AD patients (β=0.48, SE=0.21, p=0.02), but not in MCI patients when adjusted for confounders. Conclusions: We suggest that UA might be related to neuroprotective compensation for oxidative stress which would reduce the rate of cognitive decline in AD patients.
Abstract
Background: Uric acid (UA) is known to have neuroprotective effects by acting as a major plasma antioxidant. However, it is also known to be a pro-oxidant under certain circumstances. In this study, we analysed the association between UA and homocystein, which is a well-known pro-oxidant, as well as the association between UA and cognitive function in order to evaluate the neuroprotective function of UA in neurodegenerative disease progression. Methods: Plasma UA and homocystein, along with the two other major plasma antioxidants albumin and bilirubin, were measured in 133 Alzhiemer’s disease (AD) patients, 98 Mild cognitive impairment (MCI) patients, and 77 normal elderly controls. The cognitive function of the subjects was evaluated by Mini Mental Status Examination (MMSE). By using linear regression analysis, we investigated the association between UA with homocystein in each of these groups. Furthermore, the association between UA levels and the MMSE score was also analyzed. All analyses were adjusted for age, sex, education, hypertension, and diabetes mellitus. Results: Homocystein increased in MCI, AD group compared with the control group. In the AD group, there was a statistically significant increase of UA compared with the MCI group, after adjusting for age, gender, hypertension, diabetes mellitus, and education (p=0.017). Linear regression analysis showed that increasing homocystein predicted increasing UA in MCI and AD patients (β=1.12, SE=0.36, p=0.002; β=1.79, SE=0.43, p<0.001, respectively). Furthermore, increasing UA predicted increasing MMSE in AD patients (β=0.48, SE=0.21, p=0.02), but not in MCI patients when adjusted for confounders. Conclusions: We suggest that UA might be related to neuroprotective compensation for oxidative stress which would reduce the rate of cognitive decline in AD patients.
참고문헌 (26)
- Patterson RA, "Prooxidant and antioxidant properties of human serum ultrafiltrates toward LDL: important role of uric acid", J Lipid Res, 44, pp.521~521 (2003)
- Maxwell SR, "Antioxidant status in patients with uncomplicated insulin-dependent and non-insulin dependent diabetes mellitus", Eur J Clin Invest, 27, pp.484~490 (1997)
- Becker BF, "Towards the physiological function of uric acid", Free Radic Biol Med, 14, pp.615~631 (1993)
- 배치운, "Decreased plasma antioxidants in patients with Alzheimer's disease", INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, 21, pp.344~348, JOHN WILEY & SONS LTD
- Rinaldi P, "Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer’s disease", Neurobiol Aging, 24, pp.915~919 (2003)
- Li J, "Association of cognitive function with serum uric acid level among Chinese nonagenarians and centenarians", Exp Gerontol, 45, pp.331~335 (2010)
- Irizarry MC, "Plasma urate and progression of mild cognitive impairment", Neurodegener Dis, 6, pp.23~28 (2009)
- Schretlen DJ, "Serum uric acid and cognitive function in community-dwelling older adults", Neuropsychology, 21, pp.136~140 (2007)
- Vannorsdall TD, "Cerebral ischemia mediates the effect of serum uric acid on cognitive function", Stroke, 39, pp.3418~3420 (2008)
- Cherubini A, "Antioxidant profile and early outcome in stroke patients", Stroke, 31, pp.2295~2300 (2000)
- McKhan G, "Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer’s disease", Neurology, 34, pp.939~944 (1984)
- Petersen RC, "Current concepts in mild cognitive impairment", Arch Neurol, 58, pp.1985~1992 (2001)
- Kang Y, "Seoul Neuropsychological Screening Battery (SNSB)" (2003), Human Brain Research & Consulting Co
- Robbins TW, "A study of performance on tests from the CANTAB battery sensitive to frontal lobe dysfunction in a large sample of normal volunteers: implications for theories of executive functioning and cognitive aging. Cambridge neuropsychological test automated battery", J Int Neuropsychol Soc, 4, pp.474~490 (1998)
- Hink HU, "Peroxidase properties of extracellular superoxide dismutase: role of uric acid in modulating in vivo activity", Arterioscler Thromb Vasc Biol, 22, pp.1402~1408 (2002)
- Hayden MR, "Uric acid: A new look at an old risk marker for cardiovascular disease, metabolic syndrome, and type 2 diabetes mellitus: the urate redox shuttle", Nutr Metlab, 19, pp.1~10 (2004)
- Yu ZF, "Uric acid protects neurons against excitotoxic and metabolic insults in cell culture, and against focal ischemic brain injury in vivo", J Neurosci Res, 53, pp.613~625 (1998)
- Kono H, "Uric acid promotes an acute inflammatory response to sterile cell death in mice", J Clin Invest, 120, pp.1939~1949 (2010)
- Euser SM, "Serum uric acid and cognitive function and dementia", Brain, 132(2), pp.377~382 (2009)
- Schretlen DJ, "Serum uric acid and brain ischemia in normal elderly adults", Neurology, 69, pp.1418~1423 (2007)
- Bos MJ, "Uric acid is a risk factor for myocardial infarction and stroke; The Rotterdam Study", Stroke, 37, pp.1503~ (2006)
- Seshadri S, "Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease", N Engl J Med, 346, pp.476~483 (2002)
- 조선영, "알츠하이머병, 혈관성 치매 및 경도인지장애와 호모시스테인 농도 증가의 연관성", 대한신경과학회지, 24(3), pp.231~238 (2006), 대한신경과학회
- Herrmann W, "Homocysteine: a biomarker in neurodegenerative disease", Clin Chem Lab Med, 49, pp.435~441 (2011)
- 윤보라, "알츠하이머병에서 백질 변화 정도에 따른 혈중 요산수치", Dementia and Neurocognitive Disorders(대한치매학회지), 8(2), pp.79~83 (2009), 대한치매학회
- Nunomura A, "Oxidative damage is the earliest event in Alzheimer’s disease", J Neuropathol Exp Neurol, 60, pp.759~767 (2001)