时间标签：数据日期 2026-10-31 · 生成时间 2026-11-01 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/28–2026/10/31 ｜ 情报发生日期 2026-10-31
研究问题
In this study, we aimed to define lipid profiles in the cerebrospinal fluid (CSF) and plasma samples from cognitively unimpaired participants aged over 65 years in the Mayo Clinic Study of Aging (MCSA) using shotgun lipidomics.
方法
CSF or plasma samples from cognitively unimpaired participants (CDR global score = 0, >65 years old) with available APOE genotype were obtained from the MCSA or the Knight Alzheimer's Disease Research Center (ADRC) at Washington University (WashU) School of Medicine in St.；Among the cohort, longitudinal CDR conversion analysis included cases with CDR Sum of Boxes (CDR‐SB) = 0 at the baseline visit and at least one follow‐up visit for cognitive testing.；The MCSA includes participants from Olmsted County, Minnesota, USA.；Research participants enrolled in studies of memory and aging at the Knight ADRC consisted of community‐dwelling older adults including participants with and without cognitive impairment, who were recruited primarily from the greater St.
核心结论
For all analyses, APOE genotype was categorized into three groups: APOE2 (ε2/ε3, N = 39), APOE3 (ε3/ε3, N = 171), or APOE4 (ε3/ε4 or ε4/ε4, N = 72) (Table ).；While CSF levels of Aβ42 and SNAP25 differed significantly between the three APOE genotype groups (p < 0.001), the effects on plasma biomarkers were modest (Tables and ).；Using shotgun lipidomics, we identified and quantified 145 lipid species across 11 different lipid classes including cholesterol esters (CEs), non‐esterified fatty acids (FAs), total cholesterol (TC), lysophosphatidylcholine (LPC), phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylserine (PS), sphingomyelin (SM), and triacylglycerol (TAG) in CSF and plasma samples. ‖ 结论：Since our findings are based on cohorts with relatively less diversity, further studies are required to confirm our findings in more diverse populations.
局限
Future studies should also dissect potentially different roles of TAG depending on their acyl chain compositions in the development of metabolic syndrome and age‐related cognitive decline.；Excess TAG accumulates in intracellular spaces beyond their metabolic capacity may instead cause lipotoxicity, although further studies are needed.；Further studies to determine how APOE4 alters TAG balance between brain and blood may provide a clue for better understanding of the pathogenic mechanisms by which APOE4 increases the risk of cognitive impairment and AD.
对本项目的价值
★★☆☆☆ 脑老化是最大未满足需求，也是终点最难量化的领域；biomarker 与认知读数选择最敏感。
全文来源
PMC JATS 全文（正文 42,635 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：CSF and plasma lipid profiling predicts risk of cognitive impairment in cognitively unimpaired older adults.
- 期刊与标识：Alzheimers Dement · PMID 42947286 · DOI 10.1002/alz.71924
A 级证据分级：A 级（同行评议人体研究）
本文属人体研究证据，但需注意：观察性或小样本干预的结论不等于已证实临床获益；效应量与长期安全性仍需更大规模、更长随访的试验验证。
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