血清β-突触核蛋白与血液生物标志物及脑萎缩的关系。

Relationship of serum beta-synuclein with blood biomarkers and brain atrophy.

作者信息

Oeckl Patrick, Anderl-Straub Sarah, Danek Adrian, Diehl-Schmid Janine, Fassbender Klaus, Fliessbach Klaus, Halbgebauer Steffen, Huppertz Hans-Jürgen, Jahn Holger, Kassubek Jan, Kornhuber Johannes, Landwehrmeyer Bernhard, Lauer Martin, Prudlo Johannes, Schneider Anja, Schroeter Matthias L, Steinacker Petra, Volk Alexander E, Wagner Matias, Winkelmann Juliane, Wiltfang Jens, Ludolph Albert C, Otto Markus

机构信息

Department of Neurology, Ulm University Hospital, Ulm, Germany.

German Center for Neurodegenerative Diseases (DZNE e.V.), Ulm, Germany.

出版信息

Alzheimers Dement. 2023 Apr;19(4):1358-1371. doi: 10.1002/alz.12790. Epub 2022 Sep 21.

DOI:10.1002/alz.12790

PMID:36129098

Abstract

BACKGROUND

Recent data support beta-synuclein as a blood biomarker to study synaptic degeneration in Alzheimer's disease (AD).

METHODS

We provide a detailed comparison of serum beta-synuclein immunoprecipitation - mass spectrometry (IP-MS) with the established blood markers phosphorylated tau 181 (p-tau181) (Simoa) and neurofilament light (NfL) (Ella) in the German FTLD consortium cohort (n = 374) and its relation to brain atrophy (magnetic resonance imaging) and cognitive scores.

RESULTS

Serum beta-synuclein was increased in AD but not in frontotemporal lobar degeneration (FTLD) syndromes. Beta-synuclein correlated with atrophy in temporal brain structures and was associated with cognitive impairment. Serum p-tau181 showed the most specific changes in AD but the lowest correlation with structural alterations. NfL was elevated in all diseases and correlated with frontal and temporal brain atrophy.

DISCUSSION

Serum beta-synuclein changes differ from those of NfL and p-tau181 and are strongly related to AD, most likely reflecting temporal synaptic degeneration. Beta-synuclein can complement the existing panel of blood markers, thereby providing information on synaptic alterations.

HIGHLIGHTS

Blood beta-synuclein is increased in Alzheimer's disease (AD) but not in frontotemporal lobar degeneration (FTLD) syndromes. Blood beta-synuclein correlates with temporal brain atrophy in AD. Blood beta-synuclein correlates with cognitive impairment in AD. The pattern of blood beta-synuclein changes in the investigated diseases is different to phosphorylated tau 181 (p-tau181) and neurofilament light (NfL).

摘要

背景

近期数据支持β-突触核蛋白作为一种血液生物标志物，用于研究阿尔茨海默病（AD）中的突触变性。

方法

我们在德国额颞叶痴呆（FTLD）联盟队列（n = 374）中，对血清β-突触核蛋白免疫沉淀-质谱法（IP-MS）与已确立的血液标志物磷酸化tau 181（p-tau181）（Simoa法）和神经丝轻链（NfL）（Ella法）进行了详细比较，并研究了其与脑萎缩（磁共振成像）和认知评分的关系。

结果

AD患者血清β-突触核蛋白升高，而额颞叶痴呆（FTLD）综合征患者则未升高。β-突触核蛋白与颞叶脑结构萎缩相关，并与认知障碍有关。血清p-tau181在AD中显示出最特异的变化，但与结构改变的相关性最低。NfL在所有疾病中均升高，并与额叶和颞叶脑萎缩相关。

讨论

血清β-突触核蛋白的变化与NfL和p-tau181不同，且与AD密切相关，很可能反映了颞叶突触变性。β-突触核蛋白可以补充现有的血液标志物组合，从而提供有关突触改变的信息。

要点

阿尔茨海默病（AD）患者血液中的β-突触核蛋白升高，而额颞叶痴呆（FTLD）综合征患者则未升高。AD患者血液中的β-突触核蛋白与颞叶脑萎缩相关。AD患者血液中的β-突触核蛋白与认知障碍相关。在所研究疾病中，血液β-突触核蛋白的变化模式与磷酸化tau 181（p-tau181）和神经丝轻链（NfL）不同。