脂质体
脑脊液
脂类学
痴呆
鞘磷脂
内科学
病理生理学
病态的
多发性硬化
β淀粉样蛋白
磷脂酰乙醇胺
神经酰胺
内分泌学
疾病
医学
脂质代谢
胆固醇
生物信息学
化学
生物
生物化学
精神科
磷脂
磷脂酰胆碱
细胞凋亡
膜
作者
Farida Dakterzada,Mariona Jové,Raquel Huerto,Anna Carnes,Joaquím Sol,Reinald Pamplona,Gerard Piñol‐Ripoll
出处
期刊:GeroScience
[Springer Nature]
日期:2023-11-24
被引量:1
标识
DOI:10.1007/s11357-023-00989-x
摘要
Genetic, metabolic, and clinical evidence links lipid dysregulation to an increased risk of Alzheimer's disease (AD). However, the role of lipids in the pathophysiological processes of AD and its clinical progression is unclear. We investigated the association between cerebrospinal fluid (CSF) lipidome and the pathological hallmarks of AD, progression from mild cognitive impairment (MCI) to AD, and the rate of cognitive decline in MCI patients. The CSF lipidome was analyzed by liquid chromatography coupled to mass spectrometry in an LC-ESI-QTOF-MS/MS platform for 209 participants: 91 AD, 92 MCI, and 26 control participants. The MCI patients were followed up for a median of 58 (± 12.5) months to evaluate their clinical progression to AD. Forty-eight (52.2%) MCI patients progressed to AD during follow-up. We found that higher CSF levels of hexacosanoic acid and ceramide Cer(d38:4) were associated with an increased risk of amyloid beta 42 (Aβ42) positivity in CSF, while levels of phosphatidylethanolamine PE(40:0) were associated with a reduced risk. Higher CSF levels of sphingomyelin SM(30:1) were positively associated with pathological levels of phosphorylated tau in CSF. Cholesteryl ester CE(11D3:1) and an unknown lipid were recognized as the most associated lipid species with MCI to AD progression. Furthermore, TG(O-52:2) was identified as the lipid most strongly associated with the rate of progression. Our results indicate the involvement of membrane and intracellular neutral lipids in the pathophysiological processes of AD and the progression from MCI to AD dementia. Therefore, CSF neutral lipids can be used as potential prognostic markers for AD.
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