지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2011.1
- 수록면
- 10 - 18 (9page)
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초록· 키워드
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The failure of large-scale drug trials targeting the amyloidogenic pathway in Alzheimer’s disease (AD) is increasing the need to identify a novel pathogenic mechanism. Studies finding a relationship between sporadic AD and type-2 diabetes mellitus (T2DM) are now receiving more attention. The risk for developing both T2DM and sporadic AD increases exponentially with age, and having T2DM doubles the risk of developing AD. The postmortem brains of AD patients show altered activities of insulin receptors and downstream molecules, as well as reduced protein and mRNA levels of insulin. More-recent laboratory research using animal models has identified mechanisms that are shared by diabetes and AD. Exogenous application of streptozotocin, which disrupts systemic insulin secretion, results in insulin deficiency, increased tau phosphorylation,and cognitive impairments that can be reversed by exogenous insulin supplementation. However, AD pathology is more severe in T2DM animal models exhibiting hyperinsulinemia and insulin resistance, and this is not modulated by insulin. The symptoms of this AD pathology included increased tau phosphorylation at multiple sites, increased tau cleavage, and greater neuronal and synaptic damage, even with increased amyloid β protein production. It has therefore been suggested that hyperinsulinemia and insulin resistance represent major factors underlying AD in T2DM. A recent study involving cross-mating ob/ob and amyloid precursor protein transgenic mice provided evidence that T2DM and AD aggravate each other, and suggested that cerebral vessels constitute an important substrate that is commonly damaged by the two major disorders.
Given the evidence provided by animal models, further investigation of the mechanisms underlying T2DM in AD should help to identify potential treatment targets in AD.
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참고문헌 (24)
참고문헌 신청
Arvanitakis Z / 2004 / Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function / Arch Neurol 61 : 661 ~ 666
Brant AM / 1993 / Immunological analysis of glucose transporters expressed in different regions of the rat brain and central nervous system / Biochem Biophys Res Commun 192
Craft S / 1998 / Cerebrospinal fluid and plasma insulin levels in Alzheimer’s disease: relationship to severity of dementia and apolipoprotein E genotype / Neurology 50 : 1
Deng Y / 2009 / Dysregulation of insulin signaling, glucose transporters, O-GlcNAcylation, and phosphorylation of tau and neurofilaments in the brain: implication for Alzhei
Grodstein F / 2001 / Nurses’ Health Study. Type 2 diabetes and cognitive function in community-dwelling elderly women / Diabetes Care 24 : 1060 ~ 1065
Brant AM / 1993 / Immunological analysis of glucose transporters expressed in different regions of the rat brain and central nervous system / Biochem Biophys Res Commun 192
Craft S / 1998 / Cerebrospinal fluid and plasma insulin levels in Alzheimer’s disease: relationship to severity of dementia and apolipoprotein E genotype / Neurology 50 : 1
Deng Y / 2009 / Dysregulation of insulin signaling, glucose transporters, O-GlcNAcylation, and phosphorylation of tau and neurofilaments in the brain: implication for Alzhei
Grodstein F / 2001 / Nurses’ Health Study. Type 2 diabetes and cognitive function in community-dwelling elderly women / Diabetes Care 24 : 1060 ~ 1065
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