The diagnosis of Alzheimer's disease (AD) relies on the presence of amyloidosis and tauopathy, as reflected in cerebrospinal fluid (CSF), independently from the clinical stage. Recently, CSF d-serine has been proposed as a possible new AD biomarker, reflecting dysfunctional activation of neuronal glutamatergic N-methyl-d-aspartate receptor (NMDAR). In this study, we measured blood serum and CSF concentration of two NMDAR modulators, such as d-serine and d-aspartate, in a cohort of drug-free subjects encompassing the whole AD clinical spectrum. In addition, we also analyzed d-serine levels in a cohort of post-mortem AD and control cortex samples. We reported unaltered serum and CSF concentrations of d-serine and d-aspartate in AD patients both during the AD progression and compared to non-demented controls. Accordingly, no correlation was detected between serum or CSF d-serine content and mini-mental state examination or Clinical Dementia Rating. Similarly, cortical d-serine levels were also unaltered in post-mortem samples of AD patients. Overall, our results failed to confirm previous findings indicating the CSF d-serine as a novel biomarker for AD.

阿尔茨海默氏病（AD）的诊断取决于脑脊液（CSF）中反映的淀粉样变性和tauopathy的存在，而与临床阶段无关。最近，CSF d -丝氨酸已被提出作为一个可能的新的生物标志物的AD，反映神经元谷氨酸功能失调活化Ñ甲基d天冬氨酸受体（NMDAR）。在这项研究中，我们在涵盖整个AD临床范围的无药物受试者队列中测量了两种NMDAR调节剂（例如d-丝氨酸和d-天冬氨酸）的血清和CSF浓度。此外，我们还分析了一组死后的d-丝氨酸水平AD和对照皮层样本。我们报道了AD患者在AD进展期间以及与非痴呆对照组相比血清d-丝氨酸和d-天冬氨酸的血清和CSF浓度未改变。因此，在血清或CSF d-丝氨酸含量与小精神状态检查或临床痴呆评分之间未发现相关性。类似地，AD患者的尸检样品中的皮质d-丝氨酸水平也未改变。总体而言，我们的结果未能证实以前的发现，表明CSF d-丝氨酸是AD的新型生物标志物。