Brain-derived Neurotrophic Factor Is Associated with Cognitive Impairment in Elderly Korean Individuals
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Objective: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is widely expressed in the mammalian brain and acts to regulate neuronal survival and influence cognitive processes. The present study measured serum BDNF levels to investigate the associations of the BDNF Val66Met and 5-hydroxytryptamine transporter linked promoter region (5-HTTLPR) polymorphisms with cognitive function in elderly Korean individuals. Methods: Over 60 years, a total of 834 subjects were recruited for the present study. The subjects were classified into groups based on the degree of cognitive impairment (age-associated cognitive decline, mild cognitive impairment, and Alzheimer’s disease) and compared with normal controls in terms of a neuropsychological assessment and a clinical evaluation. Results: Of the initial 834 study participants, 165 (59 controls and 106 subjects with cognitive impairments) completed the study. There was a significant increase in serum BDNF levels in subjects with cognitive impairments relative to the control group and the BDNF Val66Met polymorphism was significantly associated with cognitive function but not serum BDNF levels. The 5-HTTLPR polymorphism did not have any associations with cognitive impairment or serum BDNF levels. Conclusion: The present findings suggest that BDNF may play a role in the pathophysiology of cognitive impairment and the BDNF Val66Met polymorphism may be an important factor in the susceptibility to these age-related deficits.
Abstract
Objective: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is widely expressed in the mammalian brain and acts to regulate neuronal survival and influence cognitive processes. The present study measured serum BDNF levels to investigate the associations of the BDNF Val66Met and 5-hydroxytryptamine transporter linked promoter region (5-HTTLPR) polymorphisms with cognitive function in elderly Korean individuals. Methods: Over 60 years, a total of 834 subjects were recruited for the present study. The subjects were classified into groups based on the degree of cognitive impairment (age-associated cognitive decline, mild cognitive impairment, and Alzheimer’s disease) and compared with normal controls in terms of a neuropsychological assessment and a clinical evaluation. Results: Of the initial 834 study participants, 165 (59 controls and 106 subjects with cognitive impairments) completed the study. There was a significant increase in serum BDNF levels in subjects with cognitive impairments relative to the control group and the BDNF Val66Met polymorphism was significantly associated with cognitive function but not serum BDNF levels. The 5-HTTLPR polymorphism did not have any associations with cognitive impairment or serum BDNF levels. Conclusion: The present findings suggest that BDNF may play a role in the pathophysiology of cognitive impairment and the BDNF Val66Met polymorphism may be an important factor in the susceptibility to these age-related deficits.
참고문헌 (36)
- Seshadri S., "Lifetime risk of stroke and dementia : current concepts, and estimates from the Framingham Study", Lancet Neurol, 6, pp.1106~1114 (2007)
- Ferri CP., "Global prevalence of dementia : a Delphi consensus study", Lancet, 366, pp.2112~2117 (2005)
- Bramham CR., "BDNF function in adult synaptic plasticity : the synaptic consolidation hypothesis", Prog Neurobiol, 76, pp.99~125 (2005)
- Figurov A., "Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus", Nature, 381, pp.706~709 (1996)
- Tapia-Arancibia L., "New insights into brain BDNF function in normal aging and Alzheimer disease", Brain Res Rev, 59, pp.201~220 (2008)
- Holsinger RM., "Quantitation of BDNF mRNA in human parietal cortex by competitive reverse transcription-polymerase chain reaction : decreased levels in Alzheimer's disease", Brain Res Mol Brain Res, 76, pp.347~354 (2000)
- Yasutake C., "Serum BDNF, TNF-alpha and IL-1beta levels in dementia patients : comparison between Alzheimer's disease and vascular dementia", Eur Arch Psychiatry Clin Neurosci, 256, pp.402~406 (2006)
- Laske C., "BDNF serum and CSF concentrations in Alzheimer's disease, normal pressure hydrocephalus and healthy controls", J Psychiatr Res, 41, pp.387~394 (2007)
- Yu H., "Association study of the decreased serum BDNF concentrations in amnestic mild cognitive impairment and the Val66Met polymorphism in Chinese Han", J Clin Psychiatry, 69, pp.1104~1111 (2008)
- 이정구, "Decreased Serum Brain-Derived Neurotrophic Factor Levels in Elderly Korean with Dementia", PSYCHIATRY INVESTIGATION, 6(4), pp.299~305 (2009), 대한신경정신의학회
- Ventriglia M., "Serum brain-derived neurotrophic factor levels in different neurological diseases", Biomed Res Int, 2013, pp.901082~ (2013)
- Angelucci F., "Alzheimer's disease(AD)and Mild Cognitive Impairment(MCI)patients are characterized by increased BDNF serum levels", Curr Alzheimer Res, 7, pp.15~20 (2010)
- Ventriglia M., "Association between the BDNF 196 A", G polymorphism and sporadic Alzheimer's disease, 2002, pp.7, 136~137
- Matsushita S., "Brain-derived neurotrophic factor gene polymorphisms and Alzheimer's disease", J Neural Transm, 112, pp.703~711 (2005)
- Borroni B., "Cumulative effect of COMT and 5-HTTLPR polymorphisms and their interaction with disease severity and comorbidities on the risk of psychosis in Alzheimer disease", Am J Geriatr Psychiatry, 14, pp.343~351 (2006)
- Huang EJ., "Neurotrophins : roles in neuronal development and function", Annu Rev Neurosci, 24, pp.677~736 (2001)
- Pezet S., "Brain-derived neurotrophic factor as a drug target for CNS disorders", Expert Opin Ther Targets, 8, pp.391~399 (2004)
- Hennigan A., "Neurotrophins and their receptors : roles in plasticity, neurodegeneration and neuroprotection", Biochem Soc Trans, 35, pp.424~427 (2007)
- Laske C., "Stage-dependent BDNF serum concentrations in Alzheimer's disease", J Neural Transm, 113, pp.1217~1224 (2006)
- Combarros O., "Polymorphism at codon 66 of the brain-derived neurotrophic factor gene is not associated with sporadic Alzheimer's disease", Dement Geriatr Cogn Disord, 18, pp.55~58 (2004)
- Bagnoli S., "Brain-derived neurotrophic factor genetic variants are not susceptibility factors to Alzheimer's disease in Italy", Ann Neurol, 55, pp.447~448 (2004)
- Desai P., "Investigation of the effect of brain-derived neurotrophic factor(BDNF)polymorphisms on the risk of late-onset Alzheimer's disease(AD)and quantitative measures of AD progression", Neurosci Lett, 379, pp.229~234 (2005)
- He XM., "Lack of association between the BDNF gene Val66Met polymorphism and Alzheimer disease in a Chinese Han population", Neuropsychobiology, 55, pp.151~155 (2007)
- Fehér A., "Serotonin transporter and serotonin receptor 2A gene polymorphisms in Alzheimer's disease", Neurosci Lett, 534, pp.233~236 (2013)
- Polito L., "A novel study and meta-analysis of the genetic variation of the serotonin transporter promoter in the italian population do not support a large effect on Alzheimer's disease risk", Int J Alzheimers Dis, 2011, pp.312341~ (2011)
- Ueki A., "Serotonin transporter gene polymorphism and BPSD in mild Alzheimer's disease", J Alzheimers Dis, 12, pp.245~253 (2007)
- Albani D., "The serotonin transporter promoter polymorphic region is not a risk factor for Alzheimer's disease related behavioral disturbances", J Alzheimers Dis, 18, pp.125~130 (2009)
- Egan MF., "The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function", Cell, 112, pp.257~269 (2003)
- Hariri AR., "Brain-derived neurotrophic factor val66met polymorphism affects human memoryrelated hippocampal activity and predicts memory performance", J Neurosci, 23, pp.6690~6694 (2003)
- "Mol Psychiatry", 2010, 116~118
- Bicalho MA., "Sociodemographic characteristics, clinical factors, and genetic polymorphisms associated with Alzheimer's disease", Int J Geriatr Psychiatry, 28, pp.640~646 (2013)
- Xu C., "Effects of BDNF Val66Met polymorphism on brain metabolism in Alzheimer's disease", Neuroreport, 21, pp.802~807 (2010)
- Connor B., "Brain-derived neurotrophic factor is reduced in Alzheimer's disease", Brain Res Mol Brain Res, 49, pp.71~81 (1997)
- Harris SE., "The brain-derived neurotrophic factor Val66Met polymorphism is associated with age-related change in reasoning skills", Mol Psychiatry, 11, pp.505~513 (2006)
- Nagata T., "Association between BDNF polymorphism(Val66Met)and executive function in patients with amnestic mild cognitive impairment or mild Alzheimer disease", Dement Geriatr Cogn Disord, 33, pp.266~272 (2012)
- Voineskos AN., "The brain-derived neurotrophic factor Val66Met polymorphism and prediction of neural risk for Alzheimer disease", Arch Gen Psychiatry, 68, pp.198~206 (2011)
