Disruptions of brain metabolism are considered integral to the pathogenesis of dementia, but thus far little is known of how dementia with Lewy bodies (DLB) impacts the brain metabolome. DLB is less well known than other neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease which is perhaps why it is under-investigated. This exploratory study aimed to address current knowledge gaps in DLB research and search for potentially targetable biochemical pathways for therapeutics. It also aimed to better understand metabolic similarities and differences with other dementias. Combined metabolomic analyses of ¹H NMR and tandem mass spectrometry of neocortical post-mortem brain tissue (Brodmann region 7) from autopsy confirmed cases of DLB (n=15) were compared with age/gender-matched, non-cognitively impaired healthy controls (n=30). Following correction for multiple comparisons, only 2 metabolites from a total of 219 measured compounds significantly differed. Putrescine was suppressed (55.4%) in DLB and O-phosphocholine was elevated (52.5%). We identified a panel of 5 metabolites (PC aa C38:4, O-Phosphocholine, putrescine, 4-Aminobutyrate, and SM C16:0) capable of accurately discriminating between DLB and control subjects. Deep Learning (DL) provided the best predictive model following 10-fold cross validation (AUROC (95% CI) = 0.80 (0.60-1.0)) with sensitivity and specificity equal to 0.92 and 0.88, respectively. Altered brain levels of putrescine and O-phosphocholine indicate that the Kennedy pathway and polyamine metabolism are perturbed in DLB. These are accompanied by a consistent underlying trend of lipid dysregulation. As yet it is unclear whether these are a cause or consequence of DLB onset.

脑代谢紊乱被认为是痴呆症发病机制不可或缺的一部分，但迄今为止，人们对路易体痴呆 (DLB) 对脑代谢组的影响知之甚少。DLB 不如阿尔茨海默氏症和帕金森氏症等其他神经退行性疾病广为人知，这也许是对其研究不足的原因。这项探索性研究旨在解决 DLB 研究中当前的知识空白，并寻找潜在的靶向生化治疗途径。它还旨在更好地了解与其他痴呆症的代谢异同。^{1 的}联合代谢组学分析将来自尸检证实的 DLB 病例（n = 15）的新皮质死后脑组织（布罗德曼区域 7）的 H NMR 和串联质谱与年龄/性别匹配、非认知受损的健康对照（n = 30）进行比较。在对多重比较进行校正后，总共 219 种测量化合物中只有 2 种代谢物存在显着差异。DLB 中的腐胺被抑制 (55.4%)，O-磷酸胆碱升高 (52.5%)。我们确定了一组 5 种代谢物（PC aa C38:4、O-磷酸胆碱、腐胺、4-氨基丁酸和 SM C16:0），能够准确区分 DLB 和对照受试者。深度学习 (DL) 在 10 倍交叉验证（AUROC (95% CI) = 0.80 (0.60-1.0)）后提供了最佳预测模型，灵敏度和特异性分别等于 0.92 和 0.88。大脑中腐胺和 O-磷酸胆碱水平的改变表明肯尼迪通路和多胺代谢在 DLB 中受到干扰。这些伴随着脂质失调的一致潜在趋势。目前尚不清楚这些是 DLB 发作的原因还是结果。