脑脊液 α-突触核蛋白实时液滴震荡转换分析在路易体痴呆前驱期轻度认知障碍中的诊断价值。

Diagnostic Value of the CSF α-Synuclein Real-Time Quaking-Induced Conversion Assay at the Prodromal MCI Stage of Dementia With Lewy Bodies.

机构信息

From IRCCS (M.R., S.B., C.Q., A.M., M.S.-M., C.Z., S.C., P.P.), Istituto delle Scienze Neurologiche di Bologna; Department of Experimental, Diagnostic and Specialty Medicine (S.B., P.P.) and Department of Biomedical and Neuromotor Sciences (L.S., S.C.), University of Bologna, Italy; Neurochemistry Laboratory, Department of Clinical Chemistry (C.E.T.), and Department of Neurology (M.v.d.B., W.M.V.d.F., A.W.L.), Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and LPVD (B.C.), Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT.

出版信息

Neurology. 2021 Aug 31;97(9):e930-e940. doi: 10.1212/WNL.0000000000012438. Epub 2021 Jul 1.

DOI:10.1212/WNL.0000000000012438

PMID:34210822

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8408510/

Abstract

OBJECTIVE

To investigate whether the CSF α-synuclein (α-syn) real-time quaking-induced conversion (RT-QuIC) assay accurately identifies patients with mild cognitive impairment (MCI) due to probable Lewy body (LB) disease.

METHODS

We applied α-syn RT-QuIC to 289 CSF samples obtained from 2 independent cohorts, including 81 patients with probable MCI-LB (age 70.7 ± 6.6 years, 13.6% female, Mini-Mental State Examination [MMSE] score 26.1 ± 2.4), 120 with probable MCI due to Alzheimer disease (AD) (age 68.6 ± 7.4 years, 45.8% female, MMSE score 25.5 ± 2.8), and 30 with unspecified MCI (age 65.4 ± 9.3 years, 30.0% female, MMSE score 27.0 ± 3.0). Fifty-eight individuals with no cognitive decline or evidence of neurodegenerative disease and 121 individuals lacking brain α-syn deposits at the neuropathologic examination were used as controls.

RESULTS

RT-QuIC identified patients with MCI-LB against cognitively unimpaired controls with 95% sensitivity, 97% specificity, and 96% accuracy and showed 98% specificity in neuropathologic controls. The accuracy of the test for MCI-LB was consistent between the 2 cohorts (97.3% vs 93.7%). Thirteen percent of patients with MCI-AD also had a positive test; of note, 44% of them developed 1 core or supportive clinical feature of dementia with Lewy bodies (DLB) at follow-up, suggesting an underlying LB copathology.

CONCLUSIONS

These findings indicate that CSF α-syn RT-QuIC is a robust biomarker for prodromal DLB. Further studies are needed to fully explore the added value of the assay to the current research criteria for MCI-LB.

CLASSIFICATION OF EVIDENCE

This study provides Class III evidence that CSF α-syn RT-QuIC accurately identifies patients with MCI-LB.

摘要

目的

探究脑脊液α-突触核蛋白（α-syn）实时液滴震荡转化（RT-QuIC）检测是否能准确识别出可能由路易体（LB）病引起的轻度认知障碍（MCI）患者。

方法

我们对来自两个独立队列的 289 份脑脊液样本进行了α-syn RT-QuIC 检测，包括 81 例可能由 LB 病引起的 MCI-LB 患者（年龄 70.7 ± 6.6 岁，13.6%为女性，简易精神状态检查量表[MMSE]评分 26.1 ± 2.4）、120 例可能由阿尔茨海默病（AD）引起的 MCI 患者（年龄 68.6 ± 7.4 岁，45.8%为女性，MMSE 评分 25.5 ± 2.8）和 30 例未明确 MCI 患者（年龄 65.4 ± 9.3 岁，30.0%为女性，MMSE 评分 27.0 ± 3.0）。58 名认知能力无下降或无神经退行性疾病证据的个体和 121 名神经病理学检查未见脑α-syn 沉积的个体作为对照组。

结果

RT-QuIC 对 MCI-LB 患者的识别灵敏度为 95%、特异性为 97%、准确性为 96%，对神经病理学对照组的特异性为 98%。该检测方法在两个队列中的准确性是一致的（97.3% vs 93.7%）。13%的 MCI-AD 患者也有阳性检测结果；值得注意的是，其中 44%在随访中出现了一个或多个支持性的路易体痴呆（DLB）临床特征，表明存在潜在的 LB 共病。