One-Carbon Metabolism in Alzheimer's Disease and Parkinson's Disease Brain Tissue.
One-Carbon Metabolism in Alzheimer's Disease and Parkinson's Disease Brain Tissue.
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DOI：
10.3390/nu14030599
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发表时间：
2022-01-29
期刊：
影响因子：
5.9
通讯作者：
Bottiglieri T
中科院分区：
文献类型：
--
作者：
Kalecký K;Ashcraft P;Bottiglieri T
一碳代谢的破坏和高同型半胱氨酸的升高先前已经被牵连在与阿尔茨海默病（AD）和帕金森病（PD）相关的痴呆的发展中。此外，PD诊断本身就有患痴呆症的风险。这是第一项直接在人类大脑额叶皮层（认知的主要中心）中探索AD和PD中一碳代谢变化的研究。应用靶向液相色谱-串联质谱法（LC-MS/MS），我们分析了从136名受试者（35 AD，65 PD，36对照）获得的尸检样本。我们发现一碳代谢物的变化表明，在AD和PD痴呆患者中，胱硫醚β-合酶（CBS）的激活效率低下，后者似乎伴随着受限的再甲基化流。已知左旋多巴-卡比多巴会减少可用的维生素B6，这可以解释CBS活性受阻的原因。我们目前的证据表明，暂时的非蛋白结合同型半胱氨酸积累左旋多巴摄入后，在大脑中的PD受试者痴呆，但不是在非痴呆的PD受试者。重要的是，这种同型半胱氨酸升高与左旋多巴剂量、疾病进展或组织病理学标志物无关，而仅与痴呆状态有关。我们假设左旋多巴诱导的效应是PD患者中再甲基化能力降低的易感受试者痴呆的直接原因。此外，我们表明，甜菜碱与认知评分最好的相关性，即使在PD受试者单独和讨论营养建议，以改善一碳代谢功能。
Disruptions in one-carbon metabolism and elevated homocysteine have been previously implicated in the development of dementia associated with Alzheimer’s disease (AD) and Parkinson’s disease (PD). Moreover, a PD diagnosis itself carries substantial risk for the development of dementia. This is the first study that explores alterations in one-carbon metabolism in AD and PD directly in the human brain frontal cortex, the primary center of cognition. Applying targeted liquid chromatography–tandem mass spectrometry (LC-MS/MS), we analyzed post-mortem samples obtained from 136 subjects (35 AD, 65 PD, 36 controls). We found changes in one-carbon metabolites that indicate inefficient activation of cystathionine β-synthase (CBS) in AD and PD subjects with dementia, the latter seemingly accompanied by a restricted re-methylation flow. Levodopa–carbidopa is known to reduce available vitamin B6, which would explain the hindered CBS activity. We present evidence of temporary non-protein-bound homocysteine accumulation upon levodopa intake in the brain of PD subjects with dementia but not in non-demented PD subjects. Importantly, this homocysteine elevation is not related to levodopa dosage, disease progression, or histopathological markers but exclusively to the dementia status. We hypothesize that this levodopa-induced effect is a direct cause of dementia in PD in susceptible subjects with reduced re-methylation capacity. Furthermore, we show that betaine best correlates with cognitive score even among PD subjects alone and discuss nutritional recommendations to improve one-carbon metabolism function.
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影响因子：
120.7
作者：
Graham, IM;Daly, LE;Andria, G
通讯作者：
Andria, G
影响因子：
9.9
作者：
Aarsland, D;Andersen, K;Kragh-Sorensen, P
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影响因子：
4.2
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Ball, M;Braak, H;Khachaturian, Z
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Khachaturian, Z
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
DOI：
10.1016/s0006-291x(02)00422-9
发表时间：
2002-05-24
影响因子：
3.1
作者：
Eto, K;Asada, T;Kimura, H
通讯作者：
Kimura, H