CSF proteins and resting-state functional connectivity in Parkinson disease
CSF proteins and resting-state functional connectivity in Parkinson disease
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DOI：
10.1212/wnl.0000000000001681
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发表时间：
2015-06-16
期刊：
影响因子：
9.9
通讯作者：
Perlmutter, Joel S.
中科院分区：
文献类型：
--
作者：
Campbell, Meghan C.;Koller, Jonathan M.;Perlmutter, Joel S.
目的：本研究的目的是探讨MRI测量的静息态功能连接中断与（rs-fcMRI）脑网络和反映帕金森病（PD）脑病理学的潜在致病蛋白的CSF水平。没有痴呆的PD参与者（n = 43）和年龄匹配的对照组（n = 22）进行腰椎穿刺以测量CSF蛋白水平，匹兹堡化合物B（PiB）-PET成像，以及停药时的rs-fcMRI。成像分析集中在5个主要的静息状态网络以及striatum.Results：参与者与PD有显着减少感觉运动功能的连接，这与CSF中的α-突触核蛋白水平降低。PD组还具有显著更强的默认模式网络功能连接，其与CSF β-淀粉样蛋白（A β）（42）或PiB摄取无关。相比之下，对照组的默认模式网络功能连接与CSF A β（42）水平相关。功能连接是相似的组之间的背侧的注意，控制，和salience network.Conclusion：这些结果表明，异常的α-突触核蛋白的积累，但不是A β，有助于破坏运动相关的功能连接在PD。此外，将CSF蛋白测量与静息状态网络的强度相关联，提供了异常α-突触核蛋白代谢与PD脑功能受损之间的直接联系。
Objective: The purpose of this study was to investigate the relationship between disruption of MRI-measured resting-state functional connectivity (rs-fcMRI) brain networks and CSF levels of potentially pathogenic proteins that reflect brain pathology in Parkinson disease (PD).Methods: PD participants without dementia (n = 43) and age-matched controls (n = 22) had lumbar punctures to measure CSF protein levels, Pittsburgh compound B (PiB)-PET imaging, and rs-fcMRI while off medication. Imaging analyses focused on 5 major resting-state networks as well as the striatum.Results: Participants with PD had significantly reduced sensorimotor functional connectivity, which correlated with reduced CSF levels of alpha-synuclein. The PD group also had significantly stronger default mode network functional connectivity that did not correlate with CSF beta-amyloid (A beta)(42) or PiB uptake. In contrast, default mode network functional connectivity in the control group did correlate with CSF A beta(42) levels. Functional connectivity was similar between groups in the dorsal attention, control, and salience networks.Conclusion: These results suggest that abnormal alpha-synuclein accumulation, but not A beta, contributes to the disruption of motor-related functional connectivity in PD. Furthermore, correlating CSF protein measures with the strength of resting-state networks provides a direct link between abnormal alpha-synuclein metabolism and disrupted brain function in PD.