Anagnostakis Filippos, Kokkorakis Michail, Walker Keenan A, Davatzikos Christos
Department of Medical and Surgical Sciences, Alma Mater University of Bologna, 40126 Bologna, Italy.
Centre for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Biomedicines. 2024 Apr 23;12(5):941. doi: 10.3390/biomedicines12050941.
Dementia poses a substantial global health challenge, warranting an exploration of its intricate pathophysiological mechanisms and potential intervention targets. Leveraging multi-omic technology, this study utilizes data from 2251 participants to construct classification models using lipidomic, gut metabolomic, and cerebrospinal fluid (CSF) proteomic markers to distinguish between the states of cognitive decline, namely, the cognitively unimpaired state, mild cognitive impairment, and dementia. The analysis identifies three CSF proteins (apolipoprotein E, neuronal pentraxin-2, and fatty-acid-binding protein), four lipids (DEDE.18.2, DEDE.20.4, LPC.O.20.1, and LPC.P.18.1), and five serum gut metabolites (Hyodeoxycholic acid, Glycohyodeoxycholic acid, Hippuric acid, Glyceric acid, and Glycodeoxycholic acid) capable of predicting dementia prevalence from cognitively unimpaired participants, achieving Area Under the Curve (AUC) values of 0.879 (95% CI: 0.802-0.956), 0.766 (95% CI: 0.700-0.835), and 0.717 (95% CI: 0.657-0.777), respectively. Furthermore, exclusively three CSF proteins exhibit the potential to predict mild cognitive impairment prevalence from cognitively unimpaired subjects, with an AUC of 0.760 (95% CI: 0.691-0.828). In conclusion, we present novel combinations of lipids, gut metabolites, and CSF proteins that showed discriminative abilities between the states of cognitive decline and underscore the potential of these molecules in elucidating the mechanisms of cognitive decline.
痴呆症是一项重大的全球健康挑战，有必要对其复杂的病理生理机制和潜在干预靶点进行探索。本研究利用多组学技术，使用来自2251名参与者的数据，构建了分类模型，采用脂质组学、肠道代谢组学和脑脊液（CSF）蛋白质组学标记物来区分认知衰退状态，即认知未受损状态、轻度认知障碍和痴呆症。分析确定了三种脑脊液蛋白（载脂蛋白E、神经元五聚体蛋白-2和脂肪酸结合蛋白）、四种脂质（DEDE.18.2、DEDE.20.4、LPC.O.20.1和LPC.P.18.1）以及五种血清肠道代谢物（猪去氧胆酸、甘氨猪去氧胆酸、马尿酸、甘油酸和甘氨脱氧胆酸），这些物质能够从认知未受损的参与者中预测痴呆症患病率，曲线下面积（AUC）值分别为0.879（95%置信区间：0.802-0.956）、0.766（95%置信区间：0.700-0.835）和0.717（95%置信区间：0.657-0.777）。此外，只有三种脑脊液蛋白具有从认知未受损受试者中预测轻度认知障碍患病率的潜力，AUC为0.760（95%置信区间：0.691-0.828）。总之，我们提出了脂质、肠道代谢物和脑脊液蛋白的新组合，这些组合在认知衰退状态之间显示出判别能力，并强调了这些分子在阐明认知衰退机制方面的潜力。
