CSF Aβ42 可预测早发性帕金森病痴呆。

CSF Aβ42 predicts early-onset dementia in Parkinson disease.

机构信息

From The Norwegian Centre for Movement Disorders (G.A., J.L., M.G.F., J.P.L., K.F.P.), Department of Neurology (G.A., K.F.P.), and Memory Clinic (G.A., K.F.P.), Stavanger University Hospital, Norway; Institute of Neuroscience and Physiology (K.B., H.Z., U.A.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; the Department of Neurology (O.-B.T.), Haukeland University Hospital, Bergen, Norway; Institute of Clinical Medicine (O.-B.T.), University of Bergen, Norway; and the Network for Medical Sciences (J.P.L.), University of Stavanger, Norway.

出版信息

Neurology. 2014 May 20;82(20):1784-90. doi: 10.1212/WNL.0000000000000425. Epub 2014 Apr 18.

DOI:10.1212/WNL.0000000000000425

PMID:24748671

Abstract

OBJECTIVE

To test in vivo the proposal from clinicopathologic studies that β-amyloid (Aβ) pathology shortens the time to dementia in Parkinson disease (PD), and to explore the utility of CSF Aβ and related measures as early prognostic biomarkers of dementia in an incident PD cohort.

METHODS

We assessed a population-based incident cohort of 104 patients with PD who underwent lumbar puncture at diagnosis. We analyzed CSF concentrations of Aβ42, Aβ40, and Aβ38 using a multiplexed immunoassay with electrochemiluminescence (ECL) detection and levels of Aβ42, total tau, and phosphorylated tau using ELISA. Patients were followed prospectively for 5 years. Dementia was diagnosed according to published criteria.

RESULTS

CSF levels of Aβ42 were significantly decreased in patients who developed dementia (n = 20, 19.2%) compared to those who did not (n = 84, 80.8%), as measured by ECL (-33%, p = 0.006) as well as ELISA (-36%, p < 0.001). No differences were observed for other markers. Low Aβ42 values predicted a substantially increased risk for subsequent dementia at high sensitivity (≥ 85%), with hazard ratios of 9.9 (95% confidence interval 2.3-43.5, p = 0.002) for Aβ42ECL <376 pg/mL and 7.6 (2.2-26.4, p = 0.001) for Aβ42ELISA <443 pg/mL, after adjustment for baseline age and PD-mild cognitive impairment (MCI) status. Aβ42 reductions tended to precede the onset of PD-MCI that progressed to dementia.

CONCLUSIONS

These in vivo data support the role of Aβ pathology in the etiology and highlight the potential utility of CSF Aβ42 as an early prognostic biomarker of dementia associated with PD.

摘要

目的

通过临床病理研究提出假设，即β-淀粉样蛋白（Aβ）病理学可缩短帕金森病（PD）患者发生痴呆的时间，并探索脑脊液 Aβ 及其相关指标作为 PD 发病队列中痴呆早期预后生物标志物的效用。

方法

我们评估了一个基于人群的 PD 发病队列，该队列包含 104 名患者，他们在诊断时进行了腰椎穿刺。我们使用电化学发光（ECL）检测的多重免疫分析法评估 CSF 中 Aβ42、Aβ40 和 Aβ38 的浓度，并使用 ELISA 评估 Aβ42、总 tau 和磷酸化 tau 的水平。患者前瞻性随访 5 年。根据已发表的标准诊断痴呆。

结果

与未发生痴呆的患者（84 名，80.8%）相比，发生痴呆的患者（20 名，19.2%）的 CSF 中 Aβ42 水平明显降低，这是通过 ECL（-33%，p = 0.006）和 ELISA（-36%，p < 0.001）测量的。其他标志物未观察到差异。低 Aβ42 值以高灵敏度（≥85%）预测随后发生痴呆的风险大大增加，Aβ42ECL<376 pg/mL 的危险比为 9.9（95%置信区间 2.3-43.5，p = 0.002），Aβ42ELISA<443 pg/mL 的危险比为 7.6（2.2-26.4，p = 0.001），调整基线年龄和 PD-轻度认知障碍（MCI）状态后。Aβ42 减少的趋势先于进展为痴呆的 PD-MCI 的发生。