Haddad Mohamed, Perrotte Morgane, Landri Sarra, Lepage Aurelie, Fülöp Tamàs, Ramassamy Charles
INRS-Institut Armand-Frappier, Laval, QC, Canada.
Institute of Nutrition and Functional Foods, Université Laval, Québec, QC, Canada.
J Alzheimers Dis. 2019;69(3):751-762. doi: 10.3233/JAD-181272.
Both advanced glycation end products (AGEs) N-(1-carboxymethyl)-L-lysine (CML) and pentosidine were found in the brain from Alzheimer's disease (AD) patients and were associated with the neuropathological hallmarks of AD. In AD patients, the circulating level of both AGEs remains unknown. Moreover, their levels in peripheral extracellular vesicles (EVs) and their association with AD remain to be determined. Finally, it is not known if neuronal cells can release AGEs via EVs and propagate AGEs.
To determine the levels of circulating CML and pentosidine during the progression of AD. Moreover, their levels in circulating EVs were determined and their association with the clinical cognitive scores were analyzed. Finally, we have studied the possibility that neuronal cells eliminate and transfer these AGEs through EVs.
CML and pentosidine levels were measured in serum and in circulating EVs. Released-EVs from SK-N-SH neuronal cells were isolated and CML levels were also determined.
The levels of CML in albumin-free serum proteins were higher in the early stage of AD while the levels of pentosidine remained unchanged. In contrast, the levels of CML in the EVs were lower in the moderate stage of AD. Interestingly, the levels of CML in serum were negatively correlated with the clinical cognitive scores MMSE and MoCA. For the first time, we were able to demonstrate that CML was present in EVs released from neuronal cells in culture.
Peripheral and circulating EVs levels of CML can differentiate early to moderate AD. In the brain, neuronal CML can propagate from cells-to-cells via EVs.
在阿尔茨海默病（AD）患者的大脑中发现了晚期糖基化终产物（AGEs）N-(1-羧甲基)-L-赖氨酸（CML）和戊糖苷，它们与AD的神经病理学特征相关。在AD患者中，这两种AGEs的循环水平尚不清楚。此外，它们在外周细胞外囊泡（EVs）中的水平及其与AD的关联仍有待确定。最后，尚不清楚神经元细胞是否能通过EVs释放AGEs并传播AGEs。
确定AD进展过程中循环CML和戊糖苷的水平。此外，测定它们在循环EVs中的水平，并分析其与临床认知评分的关联。最后，我们研究了神经元细胞通过EVs清除和转移这些AGEs的可能性。
测量血清和循环EVs中CML和戊糖苷的水平。分离SK-N-SH神经元细胞释放的EVs，并测定CML水平。
无白蛋白血清蛋白中CML的水平在AD早期较高，而戊糖苷的水平保持不变。相反，EVs中CML的水平在AD中期较低。有趣的是，血清中CML的水平与临床认知评分MMSE和MoCA呈负相关。我们首次能够证明CML存在于培养的神经元细胞释放的EVs中。
外周和循环EVs中CML的水平可以区分AD的早期到中期。在大脑中，神经元CML可以通过EVs在细胞间传播。
