Campbell Meghan C, Koller Jonathan M, Snyder Abraham Z, Buddhala Chandana, Kotzbauer Paul T, Perlmutter Joel S
From the Departments of Neurology (M.C.C., C.B., P.T.K., J.S.P.), Radiology (M.C.C., A.Z.S., J.S.P.), Psychiatry (J.M.K.), and Anatomy & Neurobiology (J.S.P.), and Programs in Occupational Therapy (J.S.P.) and Physical Therapy (J.S.P.), Washington University School of Medicine, St. Louis, MO.
Neurology. 2015 Jun 16;84(24):2413-21. doi: 10.1212/WNL.0000000000001681. Epub 2015 May 15.
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).
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.
Participants with PD had significantly reduced sensorimotor functional connectivity, which correlated with reduced CSF levels of α-synuclein. The PD group also had significantly stronger default mode network functional connectivity that did not correlate with CSF β-amyloid (Aβ)42 or PiB uptake. In contrast, default mode network functional connectivity in the control group did correlate with CSF Aβ42 levels. Functional connectivity was similar between groups in the dorsal attention, control, and salience networks.
These results suggest that abnormal α-synuclein accumulation, but not Aβ, 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 α-synuclein metabolism and disrupted brain function in PD.
本研究旨在探讨磁共振成像测量的静息态功能连接（rs-fcMRI）脑网络破坏与反映帕金森病（PD）脑病理学的潜在致病蛋白脑脊液水平之间的关系。
无痴呆的PD参与者（n = 43）和年龄匹配的对照组（n = 22）在停药状态下进行腰椎穿刺以测量脑脊液蛋白水平、匹兹堡化合物B（PiB）-PET成像和rs-fcMRI。成像分析聚焦于5个主要静息态网络以及纹状体。
PD参与者的感觉运动功能连接显著降低，这与脑脊液中α-突触核蛋白水平降低相关。PD组的默认模式网络功能连接也显著增强，且与脑脊液β-淀粉样蛋白（Aβ）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脑脊液Aβ42水平相关。背侧注意网络、控制网络和突显网络在两组之间的功能连接相似。
这些结果表明，α-突触核蛋白异常积累而非Aβ导致了PD中与运动相关的功能连接破坏。此外，将脑脊液蛋白测量值与静息态网络强度相关联，为PD中异常α-突触核蛋白代谢与脑功能破坏之间提供了直接联系。
