Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
School of Biological Sciences, Faculty of Science, University of Auckland, Private Bag, Auckland, New Zealand.
J Parkinsons Dis. 2024;14(5):965-976. doi: 10.3233/JPD-240075.
Localized pantothenic acid deficiencies have been observed in several neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease dementia (PDD), and Huntington's disease (HD), indicating downstream energetic pathway perturbations. However, no studies have yet been performed to see whether such deficiencies occur across the dementia with Lewy bodies (DLB) brain, or what the pattern of such dysregulation may be.
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.
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.
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.
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.
在几种神经退行性疾病中，如阿尔茨海默病（AD）、帕金森病痴呆（PDD）和亨廷顿病（HD），已经观察到局部泛酸缺乏，这表明下游能量途径受到干扰。然而，目前还没有研究来观察这种缺乏是否会发生在路易体痴呆（DLB）大脑中，或者这种失调的模式可能是什么。
首先，本研究旨在定量测定大脑十个区域的泛酸水平，以确定 DLB 中是否存在泛酸失调。其次，将泛酸改变的定位与以前在 AD、PDD 和 HD 大脑中的定位进行比较。
通过超高效液相色谱-串联质谱（UHPLC-MS/MS）测定 20 例 DLB 患者和 19 例对照者大脑十个区域的泛酸水平。采用非参数 Mann-Whitney U 检验确定病例对照差异，并计算 S 值、风险比、E 值和效应量。将结果与以前在 DLB、AD 和 HD 中获得的结果进行比较。
在十个研究的脑区中有六个脑区的泛酸水平显著降低：脑桥、黑质、运动皮层、颞中回、初级视觉皮层和海马。这种泛酸失调的程度与 AD 大脑最相似，AD 大脑的运动皮层、颞中回、初级视觉皮层和海马中的泛酸也减少。DLB 似乎与其他神经退行性疾病不同，因为它是这四种疾病中唯一在小脑中没有发现泛酸失调的疾病。
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这些疾病中观察到的不同临床途径。
