Neurochemistry Department, Clinical Chemistry, Amsterdam UMC, 1081 HV Amsterdam, The Netherlands.
Department of Neurology, Alzheimer Center Amsterdam, Amsterdam UMC, 1081 HV Amsterdam, The Netherlands.
Cells. 2020 Dec 29;10(1):38. doi: 10.3390/cells10010038.
Dementia with Lewy bodies (DLB) is a neurodegenerative disease where synaptic loss and reduced synaptic integrity are important neuropathological substrates. Neuronal Pentraxin 2(NPTX2) is a synaptic protein that drives the GABAergic inhibitory circuit. Our aim was to examine if NPTX2 cerebral spinal fluid (CSF) levels in DLB patients were altered and how these levels related to other synaptic protein levels and to cognitive function and decline. NPTX2, VGF, and α-synuclein levels were determined in CSF of cognitive healthy ( = 27), DLB ( = 48), and AD ( = 20) subjects. Multiple cognitive domains were tested, and data were compared using linear models. Decreased NPTX2 levels were observed in DLB (median = 474) and AD (median = 453) compared to cognitive healthy subjects (median = 773). Strong correlations between NPTX2, VGF, and α-synuclein were observed dependent on diagnosis. Combined, these markers had a high differentiating power between DLB and cognitive healthy subjects (AUC = 0.944). Clinically, NPTX2 levels related to global cognitive function and cognitive decline in the visual spatial domain. NPTX2 CSF levels were reduced in DLB and closely correlated to decreased VGF and α-synuclein CSF levels. CSF NPTX2 levels in DLB related to decreased functioning in the visual spatial domain.
路易体痴呆（DLB）是一种神经退行性疾病，突触丧失和突触完整性降低是重要的神经病理学基础。神经元五聚素 2（NPTX2）是一种驱动 GABA 能抑制回路的突触蛋白。我们的目的是研究 DLB 患者的 NPTX2 脑脊液（CSF）水平是否发生改变，以及这些水平与其他突触蛋白水平以及认知功能和下降的关系。 在认知健康者（=27）、DLB（=48）和 AD（=20）受试者的 CSF 中测定了 NPTX2、VGF 和 α-突触核蛋白的水平。对多个认知领域进行了测试，并使用线性模型比较了数据。与认知健康者（中位数=773）相比，DLB（中位数=474）和 AD（中位数=453）的 NPTX2 水平降低。观察到 NPTX2、VGF 和 α-突触核蛋白之间存在强相关性，与诊断有关。这些标志物联合具有区分 DLB 和认知健康者的高区分能力（AUC=0.944）。临床上，NPTX2 水平与整体认知功能和视觉空间域的认知下降有关。DLB 患者的 CSF NPTX2 水平降低，与 VGF 和 α-突触核蛋白 CSF 水平降低密切相关。DLB 患者的 CSF NPTX2 水平与视觉空间域功能下降有关。
