脑脊液β-突触核蛋白作为临床前阿尔茨海默病的突触生物标志物。

Cerebrospinal fluid β-synuclein as a synaptic biomarker for preclinical Alzheimer's disease.

作者信息

Barba Lorenzo, Abu Rumeileh Samir, Bellomo Giovanni, Paolini Paoletti Federico, Halbgebauer Steffen, Oeckl Patrick, Steinacker Petra, Massa Federico, Gaetani Lorenzo, Parnetti Lucilla, Otto Markus

机构信息

Department of Neurology, University Hospital Halle, Halle (Saale), Germany.

Section of Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.

出版信息

J Neurol Neurosurg Psychiatry. 2023 Jan;94(1):83-86. doi: 10.1136/jnnp-2022-329124. Epub 2022 Aug 9.

DOI:10.1136/jnnp-2022-329124

PMID:35944974

Abstract

INTRODUCTION

β-synuclein (β-syn) is a presynaptic protein, whose cerebrospinal fluid (CSF) levels are increased in patients with Alzheimer's diseases (AD) showing mild cognitive impairment (MCI) and dementia (dem). Here, we aimed to investigate CSF β-syn in subjects at different AD stages, including preclinical AD (pre-AD), and to compare its behaviour with another synaptic biomarker, α-synuclein (α-syn), and two biomarkers of neuro-axonal damage, namely neurofilament light chain protein (NfL) and total tau protein (t-tau).

METHODS

We measured β-syn, α-syn, t-tau and NfL in CSF of 75 patients with AD (pre-AD n=17, MCI-AD n=28, dem-AD n=30) and 35 controls (subjective memory complaints, SMC-Ctrl n=13, non-degenerative neurological disorders, Dis-Ctrl n=22).

RESULTS

CSF β-syn, α-syn, t-tau were significantly elevated in pre-AD patients compared with controls (p<0.0001, p=0.02 and p=0.0001, respectively), while NfL only increased in dem-AD (p=0.001). Pre-AD cases showed lower t-tau concentrations than MCI-AD (p=0.04) and dem-AD (p=0.01). CSF β-syn had the best diagnostic performance for the discrimination of pre-AD subjects from all controls (area under the curve, AUC=0.97) and from SMC-Ctrl subjects (AUC=0.99).

DISCUSSION

CSF β-syn increases in the whole AD continuum since the preclinical stage and represents a promising biomarker of synaptic damage in AD.

摘要

引言

β-突触核蛋白（β-syn）是一种突触前蛋白，在患有轻度认知障碍（MCI）和痴呆（dem）的阿尔茨海默病（AD）患者的脑脊液（CSF）中水平升高。在此，我们旨在研究不同AD阶段（包括临床前AD（pre-AD））受试者的脑脊液β-syn，并将其行为与另一种突触生物标志物α-突触核蛋白（α-syn）以及两种神经轴突损伤生物标志物，即神经丝轻链蛋白（NfL）和总tau蛋白（t-tau）进行比较。

方法

我们测量了75例AD患者（pre-AD n = 17，MCI-AD n = 28，dem-AD n = 30）和35名对照者（主观记忆主诉，SMC-Ctrl n = 13，非退行性神经系统疾病，Dis-Ctrl n = 22）脑脊液中的β-syn、α-syn、t-tau和NfL。

结果

与对照组相比，pre-AD患者脑脊液中的β-syn、α-syn、t-tau显著升高（分别为p < 0.0001、p = 0.02和p = 0.0001），而NfL仅在dem-AD中升高（p = 0.001）。Pre-AD病例的t-tau浓度低于MCI-AD（p = 0.04）和dem-AD（p = 0.01）。脑脊液β-syn在区分pre-AD受试者与所有对照者（曲线下面积，AUC = 0.97）以及与SMC-Ctrl受试者（AUC = 0.99）方面具有最佳诊断性能。