Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Behavioral Health Service, Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA.
Alzheimers Dement. 2020 Sep;16(9):1234-1247. doi: 10.1002/alz.12110. Epub 2020 Jul 27.
Altered lipid metabolism is implicated in Alzheimer's disease (AD), but the mechanisms remain obscure. Aging-related declines in circulating plasmalogens containing omega-3 fatty acids may increase AD risk by reducing plasmalogen availability.
We measured four ethanolamine plasmalogens (PlsEtns) and four closely related phosphatidylethanolamines (PtdEtns) from the Alzheimer's Disease Neuroimaging Initiative (ADNI; n = 1547 serum) and University of Pennsylvania (UPenn; n = 112 plasma) cohorts, and derived indices reflecting PlsEtn and PtdEtn metabolism: PL-PX (PlsEtns), PL/PE (PlsEtn/PtdEtn ratios), and PBV (plasmalogen biosynthesis value; a composite index). We tested associations with baseline diagnosis, cognition, and cerebrospinal fluid (CSF) AD biomarkers.
Results revealed statistically significant negative relationships in ADNI between AD versus CN with PL-PX (P = 0.007) and PBV (P = 0.005), late mild cognitive impairment (LMCI) versus cognitively normal (CN) with PL-PX (P = 2.89 × 10 ) and PBV (P = 1.99 × 10 ), and AD versus LMCI with PL/PE (P = 1.85 × 10 ). In the UPenn cohort, AD versus CN diagnosis associated negatively with PL/PE (P = 0.0191) and PBV (P = 0.0296). In ADNI, cognition was negatively associated with plasmalogen indices, including Alzheimer's Disease Assessment Scale 13-item cognitive subscale (ADAS-Cog13; PL-PX: P = 3.24 × 10 ; PBV: P = 6.92 × 10 ) and Mini-Mental State Examination (MMSE; PL-PX: P = 1.28 × 10 ; PBV: P = 6.50 × 10 ). In the UPenn cohort, there was a trend toward a similar relationship of MMSE with PL/PE (P = 0.0949). In ADNI, CSF total-tau was negatively associated with PL-PX (P = 5.55 × 10 ) and PBV (P = 7.77 × 10 ). Additionally, CSF t-tau/Aβ ratio was negatively associated with these same indices (PL-PX, P = 2.73 × 10 ; PBV, P = 4.39 × 10 ). In the UPenn cohort, PL/PE was negatively associated with CSF total-tau (P = 0.031) and t-tau/Aβ (P = 0.021). CSF Aβ was not significantly associated with any of these indices in either cohort.
These data extend previous studies by showing an association of decreased plasmalogen indices with AD, mild cognitive impairment (MCI), cognition, and CSF tau. Future studies are needed to better define mechanistic relationships, and to test the effects of interventions designed to replete serum plasmalogens.
阿尔茨海默病（AD）中涉及脂质代谢的改变，但机制仍不清楚。与衰老相关的循环含ω-3 脂肪酸的溶血磷脂减少，可能通过降低溶血磷脂的可用性来增加 AD 的风险。
我们测量了来自阿尔茨海默病神经影像学倡议（ADNI；n = 1547 份血清）和宾夕法尼亚大学（UPenn；n = 112 份血浆）队列的四种乙醇胺溶血磷脂（PlsEtns）和四种密切相关的磷脂乙醇胺（PtdEtns），并得出反映 PlsEtn 和 PtdEtn 代谢的指数：PL-PX（PlsEtns）、PL/PE（PlsEtn/PtdEtn 比值）和 PBV（溶血磷脂生物合成值；综合指数）。我们测试了它们与基线诊断、认知和脑脊液（CSF）AD 生物标志物的关联。
ADNI 中的结果显示，AD 与 CN 之间存在统计学上显著的负相关，PL-PX（P = 0.007）和 PBV（P = 0.005），迟发性轻度认知障碍（LMCI）与认知正常（CN）之间存在负相关，PL-PX（P = 2.89×10）和 PBV（P = 1.99×10），AD 与 LMCI 之间存在负相关 PL/PE（P = 1.85×10）。在 UPenn 队列中，AD 与 CN 诊断之间存在负相关，PL/PE（P = 0.0191）和 PBV（P = 0.0296）。在 ADNI 中，认知与溶血磷脂指数呈负相关，包括阿尔茨海默病评估量表 13 项认知子量表（ADAS-Cog13；PL-PX：P = 3.24×10；PBV：P = 6.92×10）和简易精神状态检查（MMSE；PL-PX：P = 1.28×10；PBV：P = 6.50×10）。在 UPenn 队列中，MMSE 与 PL/PE（P = 0.0949）呈相似的趋势。在 ADNI 中，CSF 总 tau 与 PL-PX（P = 5.55×10）和 PBV（P = 7.77×10）呈负相关。此外，CSF t-tau/Aβ 比值与这些相同的指数呈负相关（PL-PX，P = 2.73×10；PBV，P = 4.39×10）。在 UPenn 队列中，PL/PE 与 CSF 总 tau（P = 0.031）和 t-tau/Aβ（P = 0.021）呈负相关。CSF Aβ 与这两个队列中的任何指数都没有显著相关性。
这些数据通过显示与 AD、轻度认知障碍（MCI）、认知和 CSF tau 相关的降低的溶血磷脂指数，扩展了先前的研究。未来的研究需要更好地定义机制关系，并测试旨在补充血清溶血磷脂的干预措施的效果。
