Melbourne Dementia Research Centre, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden.
Mov Disord. 2022 May;37(5):993-1003. doi: 10.1002/mds.28958. Epub 2022 Feb 8.
Neuroinflammation is implicated in the pathophysiology of Parkinson's disease (PD) and related conditions, yet prior clinical biomarker data report mixed findings.
The aim was to measure a panel of neuroinflammatory acute phase response (APR) proteins in the cerebrospinal fluid (CSF) of participants with PD and related disorders.
Eleven APR proteins were measured in the CSF of 867 participants from the BioFINDER cohort who were healthy (612) or had a diagnosis of PD (155), multiple system atrophy (MSA) (26), progressive supranuclear palsy (PSP) (22), dementia with Lewy bodies (DLB) (23), or Parkinson's disease with dementia (PDD) (29).
CSF APR proteins were mostly unchanged in PD, with only haptoglobin and α1-antitrypsin significantly elevated compared to controls. These proteins were variably increased in the other disorders. Certain protein components yielded unique signatures according to diagnosis: ferritin and transthyretin were selectively elevated in MSA and discriminated these patients from all others. Haptoglobin was selectively increased in PSP, discriminating this disease from MSA when used in combination with ferritin and transthyretin. This panel of proteins did not correlate well with severity of motor impairment in any disease category, but several (particularly ceruloplasmin and ferritin) were associated with memory performance (Mini-Mental State Examination) in patients with DLB and PDD.
These findings provide new insights into inflammatory changes in PD and related disorders while also introducing biomarkers of potential clinical diagnostic utility. © 2022 International Parkinson and Movement Disorder Society.
神经炎症与帕金森病（PD）和相关疾病的病理生理学有关，但先前的临床生物标志物数据报告结果不一。
本研究旨在测量 PD 及相关疾病患者脑脊液（CSF）中一组神经炎症急性期反应（APR）蛋白。
在 BioFINDER 队列的 867 名参与者的 CSF 中测量了 11 种 APR 蛋白，这些参与者健康（612 人）或患有 PD（155 人）、多系统萎缩症（MSA）（26 人）、进行性核上性麻痹（PSP）（22 人）、路易体痴呆（DLB）（23 人）或帕金森病伴痴呆（PDD）（29 人）。
PD 患者的 CSF APR 蛋白大多无变化，仅触珠蛋白和α1-抗胰蛋白酶显著高于对照组。其他疾病患者的这些蛋白则不同程度升高。某些蛋白成分根据诊断具有独特的特征：铁蛋白和转甲状腺素在 MSA 中选择性升高，可将这些患者与其他患者区分开来。在 PSP 中，触珠蛋白选择性升高，与铁蛋白和转甲状腺素联合使用时，可将这种疾病与 MSA 区分开来。该蛋白组与任何疾病类别的运动障碍严重程度相关性均不佳，但一些蛋白（尤其是铜蓝蛋白和铁蛋白）与 DLB 和 PDD 患者的记忆表现（简易精神状态检查）相关。
这些发现为 PD 及相关疾病的炎症变化提供了新的见解，同时也引入了具有潜在临床诊断效用的生物标志物。
