通过脑脊液生物标志物对突触通路进行解剖，以预测阿尔茨海默病。

Dissection of synaptic pathways through the CSF biomarkers for predicting Alzheimer disease.

机构信息

From the Université de Paris INSERM U1144 (M.T., E.C., J.D., J.H., C.P.), France; Clinical Neurochemistry Laboratory (A.S., K.H., A.B., H.Z., K.B.), Sahlgrenska University Hospital; Institute of Neuroscience and Physiology (A.S., K.H., A.B., H.Z., K.B.), Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; and Center of Cognitive Neurology (E.C., J.D., J.H., C.P.), Lariboisière Fernand-Widal Hospital, APHP, Paris, France.

出版信息

Neurology. 2020 Aug 25;95(8):e953-e961. doi: 10.1212/WNL.0000000000010131. Epub 2020 Jun 25.

DOI:10.1212/WNL.0000000000010131

PMID:32586895

Abstract

OBJECTIVE

To assess the ability of a combination of synaptic CSF biomarkers to separate Alzheimer disease (AD) and non-AD disorders and to help in the differential diagnosis between neurocognitive diseases.

METHODS

This was a retrospective cross-sectional monocentric study. All participants explored with CSF assessments for neurocognitive decline were invited to participate. After complete clinical and imaging evaluations, 243 patients were included. CSF synaptic (GAP-43, neurogranin, SNAP-25 total, SNAP-25aa40, synaptotagmin-1) and AD biomarkers were blindly quantified with ELISA or mass spectrometry. Statistical analysis compared CSF levels between the various groups of AD dementias (n = 81), mild cognitive impairment (MCI)-AD (n = 30), other MCI (n = 49), other dementias (OD) (n = 49), and neurologic controls (n = 35) and their discriminatory powers.

RESULTS

All synaptic biomarkers were significantly increased in patients with MCI-AD and AD-dementia compared to the other groups. All synaptic biomarkers could efficiently discriminate AD dementias from OD (AUC ≥0.80). All but synaptotagmin were also able to discriminate patients with MCI-AD from controls (area under the curve [AUC] ≥0.85) and those with AD dementias from controls (AUC ≥0.80). Overall, CSF SNAP-25aa40 had the highest discriminative power (AUC 0.93 between patients with AD dementias and controls or OD, AUC 0.90 between those with MCI-AD and controls). Higher levels were associated with 2 alleles of ε4.

CONCLUSION

All synaptic biomarkers tested had a good discriminatory power to distinguish patients with AD abnormal CSF from those with non-AD disorders. SNAP25aa40 demonstrated the highest power to discriminate AD CSF-positive patients from patients without AD and neurologic controls in this cohort.

CLASSIFICATION OF EVIDENCE

This retrospective study provides Class II evidence that CSF synaptic biomarkers discriminate patients with AD from those without AD.

摘要

目的

评估突触脑脊液生物标志物组合分离阿尔茨海默病（AD）和非 AD 疾病的能力，并有助于神经认知疾病的鉴别诊断。

方法

这是一项回顾性的横断面单中心研究。所有探索性认知减退的 CSF 评估参与者均被邀请参加。经过全面的临床和影像学评估，共纳入 243 例患者。CSF 突触（GAP-43、神经颗粒蛋白、总 SNAP-25、SNAP-25aa40、突触结合蛋白-1）和 AD 生物标志物采用 ELISA 或质谱法进行盲法定量。统计学分析比较了 AD 痴呆组（n = 81）、轻度认知障碍（MCI）-AD 组（n = 30）、其他 MCI 组（n = 49）、其他痴呆组（n = 49）和神经对照组（n = 35）之间的 CSF 水平及其判别能力。

结果

与其他组相比，MCI-AD 和 AD 痴呆患者的所有突触生物标志物均显著升高。所有突触生物标志物均能有效区分 AD 痴呆与 OD（AUC≥0.80）。除突触结合蛋白-1 外，所有生物标志物还能区分 MCI-AD 患者与对照组（曲线下面积[AUC]≥0.85）以及 AD 痴呆患者与对照组（AUC≥0.80）。总体而言，CSF SNAP-25aa40 的判别能力最高（AD 痴呆患者与对照组或 OD 患者的 AUC 为 0.93，MCI-AD 患者与对照组的 AUC 为 0.90）。较高的水平与 ε4 的 2 个等位基因相关。