UNASSIGNED: Firstly, this study aimed to quantify pantothenic acid levels across ten regions of the brain in order to determine the localization of any pantothenic acid dysregulation in DLB. Secondly, the localization of pantothenic acid alterations was compared to that previously in AD, PDD, and HD brains.
UNASSIGNED: Pantothenic acid levels were determined in 20 individuals with DLB and 19 controls by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) across ten brain regions. Case-control differences were determined by nonparametric Mann-Whitney U test, with the calculation of S-values, risk ratios, E-values, and effect sizes. The results were compared with those previously obtained in DLB, AD, and HD.
UNASSIGNED: Pantothenic acid levels were significantly decreased in six of the ten investigated brain regions: the pons, substantia nigra, motor cortex, middle temporal gyrus, primary visual cortex, and hippocampus. This level of pantothenic acid dysregulation is most similar to that of the AD brain, in which pantothenic acid is also decreased in the motor cortex, middle temporal gyrus, primary visual cortex, and hippocampus. DLB appears to differ from other neurodegenerative diseases in being the only of the four to not show pantothenic acid dysregulation in the cerebellum.
UNASSIGNED: Pantothenic acid deficiency appears to be a shared mechanism of several neurodegenerative diseases, although differences in the localization of this dysregulation may contribute to the differing clinical pathways observed in these conditions.
Decreases in a molecule called pantothenic acid (also known as vitamin B5) have been observed in several areas of the brain in multiple dementia disease, including Alzheimer’s disease, Parkinson’s disease dementia, and Huntington’s disease. However, it is unknown whether such changes also occur in another dementia disease, dementia with Lewy bodies, which shows many of the same symptoms and molecular changes as these conditions. As such, this study was performed in order to determine if and where changes in pantothenic acid occur throughout the dementia with Lewy bodies brain. Using a methodology called liquid chromatography–mass spectrometry, which is able to measure pantothenic acid levels in a highly precise manner in brain tissues, we found that several regions of the dementia with Lewy bodies brain show decreases in pantothenic acid, including some involved in movement such as the substantia nigra and motor cortex, as well as regions associated with cognition and memory such as the hippocampus—looking most similar to the pattern of changes already seen in Alzheimer’s disease. It is possible that these changes contribute to the progression of dementia with Lewy bodies; however, further studies need to be performed to determine at what point these changes happen during the disease and how they may contribute to the development of symptoms.
■首先,这项研究旨在量化大脑十个区域的泛酸水平,以确定DLB中任何泛酸失调的定位。其次,将泛酸改变的定位与以前在AD中的定位进行了比较,PDD,和HD大脑。
■通过超高效液相色谱-串联质谱(UHPLC-MS/MS)在十个大脑区域确定了20名患有DLB的个体和19名对照的泛酸水平。病例对照差异通过非参数Mann-WhitneyU检验确定,随着S值的计算,风险比率,E值,和效果大小。将结果与以前在DLB中获得的结果进行比较,AD,和HD。
■在所研究的十个大脑区域中,有六个区域的泛酸水平显着降低:脑桥,黑质,运动皮层,颞中回,初级视觉皮层,和海马体。这种水平的泛酸失调与AD大脑最相似,其中运动皮质中的泛酸也减少,颞中回,初级视觉皮层,和海马体。DLB似乎与其他神经退行性疾病的不同之处在于,它们是四种中唯一没有在小脑中显示泛酸失调的疾病。
■泛酸缺乏似乎是几种神经退行性疾病的共同机制,尽管这种失调的定位差异可能导致在这些疾病中观察到的不同的临床途径。
在多发性痴呆疾病的大脑的几个区域观察到一种称为泛酸(也称为维生素B5)的分子减少,包括老年痴呆症,帕金森病痴呆,和亨廷顿舞蹈病.然而,目前尚不清楚这种变化是否也发生在另一种痴呆症中,路易体痴呆症,这显示了许多与这些疾病相同的症状和分子变化。因此,进行这项研究是为了确定泛酸的变化是否以及在整个路易体痴呆的大脑中发生。使用一种叫做液相色谱-质谱的方法,能够以高度精确的方式测量脑组织中的泛酸水平,我们发现路易体痴呆症的几个区域显示泛酸减少,包括一些参与运动的,如黑质和运动皮层,以及与认知和记忆相关的区域,如海马-看起来与阿尔茨海默病中已经看到的变化模式最相似。这些变化可能有助于路易体痴呆的进展;然而,需要进行进一步的研究,以确定这些变化在疾病期间发生在什么时候,以及它们如何促进症状的发展。