Association of Plasma Neurofilament Light Chain with Neocortical Amyloid-β Load and Cognitive Performance in Cognitively Normal Elderly Participants
Association of Plasma Neurofilament Light Chain with Neocortical Amyloid-β Load and Cognitive Performance in Cognitively Normal Elderly Participants
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DOI：
10.3233/jad-180025
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发表时间：
2018-01-01
影响因子：
4
通讯作者：
Martins, Ralph N.
中科院分区：
文献类型：
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作者：
Chatterjee, Pratishtha;Goozee, Kathryn;Martins, Ralph N.
背景：在神经退行性条件下，神经丝（轴突细胞骨架蛋白）的破坏可能导致神经元损伤，并释放到脑脊液和血液中。在阿尔茨海默氏病（AD）中，神经丝丝（NFL）是神经丝亚基，在脑脊液和血液中升高。对象：研究血浆NFL与临床前AD特征的关联，例如高新皮质淀粉样蛋白 - 淀粉样beta载荷（ NAL）和主观记忆投诉，以及认知正常的老年人的认知表现。方法：血浆NFL浓度是在Kerr Anglican退休村倡议中使用单分子阵列平台使用单分子阵列平台的，年龄为65 - 90年。参与者接受了一系列神经心理学测试，以评估认知表现，并被归类为低NAL（NAL-，N = 65）和高NAL（NAL+，n = 35），并通过PET进行了评估，并进一步分层为主观记忆投诉者（SMC; nnal nalal nalal smc; nnal - = 51，nnal+ = 25）和非SMC（nnal- = 14，nnal+ = 10），基于内存评估诊所 - QuestionNaire.Results：等离子体NFL与认知性能成反比。 NAL+和NAL参与者之间的NFL没有显着差异。但是，在Apoe Epsilon 4非载体中，在四分位数3和4（与四分位数1）中NFL浓度的个体中观察到了较高的NAL。此外，在NAL+参与者中，与非SMC相比，SMC的NFL趋势更高。结论：等离子体NFL与老年人的认知表现成反比。虽然血浆NFL可能无法反映具有正常全球认知的个体的NAL，但当前的观察结果表明，在AD的临床前阶段，轴突损伤的发作反映了血浆NFL的增加，可能有助于AD的发病机理。
Background: The disruption of neurofilament, an axonal cytoskeletal protein, in neurodegenerative conditions may result in neuronal damage and its release into the cerebrospinal fluid and blood. In Alzheimer's disease (AD), neurofilament light chain (NFL), a neurofilament subunit, is elevated in the cerebrospinal fluid and blood.Objective: Investigate the association of plasma NFL with preclinical-AD features, such as high neocortical amyloid-beta load (NAL) and subjective memory complaints, and cognitive performance in cognitively normal older adults.Methods: Plasma NFL concentrations were measured employing the single molecule array platform in participants from the Kerr Anglican Retirement Village Initiative in Ageing Health cohort, aged 65-90 years. Participants underwent a battery of neuropsychological testing to evaluate cognitive performance and were categorized as low NAL (NAL-, n = 65) and high NAL (NAL+, n = 35) assessed via PET, and further stratified into subjective memory complainers (SMC; nNAL- = 51, nNAL+ = 25) and non-SMC (nNAL- = 14, nNAL+ = 10) based on the Memory Assessment Clinic-Questionnaire.Results: Plasma NFL inversely correlated with cognitive performance. No significant difference in NFL was observed between NAL+ and NAL-participants; however, within APOE epsilon 4 non-carriers, higher NAL was observed in individuals with NFL concentrations within quartiles 3 and 4 (versus quartile 1). Additionally, within the NAL+ participants, SMC had a trend of higher NFL compared to non-SMC.Conclusion: Plasma NFL is inversely associated with cognitive performance in elderly individuals. While plasma NFL may not reflect NAL in individuals with normal global cognition, the current observations indicate that onset of axonal injury, reflected by increased plasma NFL, within the preclinical phase of AD may contribute to the pathogenesis of AD.