Brain fuel metabolism, aging, and Alzheimer's disease.
Brain fuel metabolism, aging, and Alzheimer's disease.
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DOI：
10.1016/j.nut.2010.07.021
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发表时间：
2011-01
期刊：
影响因子：
--
通讯作者：
Rapoport SI
中科院分区：
文献类型：
--
作者：
Cunnane S;Nugent S;Roy M;Courchesne-Loyer A;Croteau E;Tremblay S;Castellano A;Pifferi F;Bocti C;Paquet N;Begdouri H;Bentourkia M;Turcotte E;Allard M;Barberger-Gateau P;Fulop T;Rapoport SI
在两组阿尔茨海默病(AD)高危人群(apoE4携带者)和那些有AD母亲家族史的人中，大脑葡萄糖代谢降低在临床可测量的认知功能下降开始之前就存在。在体外和动物研究的新证据的支持下，这些报告表明，大脑低代谢可能是导致AD认知功能下降的神经病理级联的先导和促成因素。脑代谢低下的原因尚不清楚，但可能包括血脑屏障葡萄糖运输、糖酵解和/或线粒体功能的缺陷。目前，由于方法学的问题，无法确定无认知损害的衰老是否必然与大脑葡萄糖代谢降低有关。然而，衰老似乎增加了系统对葡萄糖利用的控制恶化的风险，这反过来又可能增加至少在某些区域大脑葡萄糖摄取下降的风险。阿尔茨海默病中大脑葡萄糖供应或代谢的恶化所起的作用不排除相反的影响，即AD中的神经退行性过程由于突触功能降低而进一步降低大脑葡萄糖代谢，从而减少能量需求，从而完成恶性循环。通过打破这一循环来降低AD风险的策略应该旨在：(I)通过改善全身葡萄糖利用来改善胰岛素敏感性，或(Ii)使用安全地诱导轻微、可持续的酮血症的方法来绕过不断恶化的大脑葡萄糖代谢。
Lower brain glucose metabolism is present before the onset of clinically-measurable cognitive decline in two groups of people at risk of Alzheimer’s disease (AD) - carriers of apoE4, and in those with a maternal family history of AD. Supported by emerging evidence from in vitro and animal studies, these reports suggest that brain hypometabolism may precede and contribute to the neuropathological cascade leading cognitive decline in AD. The reason for brain hypometabolism is unclear but may include defects in glucose transport at the blood-brain barrier, glycolysis, and/or mitochondrial function. Methodological issues presently preclude knowing with certainty whether or not aging in the absence of cognitive impairment is necessarily associated with lower brain glucose metabolism. Nevertheless, aging appears to increase the risk of deteriorating systemic control of glucose utilization which, in turn, may increase the risk of declining brain glucose uptake, at least in some regions. A contributing role of deteriorating glucose availability to or metabolism by the brain in AD does not exclude the opposite effect, i.e. that neurodegenerative processes in AD further decrease brain glucose metabolism because of reduced synaptic functionality and, hence, reduced energy needs, thereby completing a vicious cycle. Strategies to reduce the risk of AD by breaking this cycle should aim to – (i) improve insulin sensitivity by improving systemic glucose utilization, or (ii) bypass deteriorating brain glucose metabolism using approaches that safely induce mild, sustainable ketonemia.
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DOI：
10.1016/s0140-6736(20)32205-4
发表时间：
2021-04-24
期刊：
Lancet (London, England)
影响因子：
--
作者：
Scheltens P;De Strooper B;Kivipelto M;Holstege H;Chételat G;Teunissen CE;Cummings J;van der Flier WM
通讯作者：
van der Flier WM
影响因子：
4.2
作者：
BOURRE, JM;FRANCOIS, M;DURAND, G
通讯作者：
DURAND, G
影响因子：
15.8
作者：
Brayne, Carol;Gao, Lu;Matthews, Fiona E.
通讯作者：
Matthews, Fiona E.
影响因子：
2.5
作者：
BOROWSKY, IW;COLLINS, RC
通讯作者：
COLLINS, RC
DOI：
10.1016/j.plefa.2007.10.016
发表时间：
2007-11-01
影响因子：
3
作者：
Brenna, J. Thomas;Diau, Guan-Yeu
通讯作者：
Diau, Guan-Yeu