探讨 GBA1 突变与路易体痴呆之间的联系，一篇迷你综述。

Exploring the link between GBA1 mutations and Dementia with Lewy bodies, A mini-review.

机构信息

Université de Paris Cité; Centre de Neurologie Cognitive, GHU AP-HP Nord, Hôpital Lariboisière Fernand-Widal, Paris, France; INSERM U1144 Optimisation Thérapeutique en Neuropsychopharmacologie, Université de Paris Cité, France.

Centre de Neurologie Cognitive, GHU AP-HP Nord, Hôpital Lariboisière Fernand-Widal, Paris, France.

出版信息

Neurosci Biobehav Rev. 2022 Oct;141:104856. doi: 10.1016/j.neubiorev.2022.104856. Epub 2022 Sep 6.

DOI:10.1016/j.neubiorev.2022.104856

PMID:36084847

Abstract

IMPORTANCE

Dementia with Lewy bodies (DLB) is a neurodegenerative disease linked to abnormal accumulation of phosphorylated α-synuclein. GBA1 is the gene encoding the lysosomal enzyme glucocerebrosidase (GCase), whose mutations are a risk factor of DLB.

OBJECTIVE

To report all available data exploring the association between GBA1 mutations and DLB.

EVIDENCE REVIEW

All publications focused on GCase and DLB in humans between 2003 and 2022 were identified on PubMed, Cochrane and ClinicalTrials.gov.

FINDINGS

29 studies were included and confirmed the strong association between GBA1 mutations and DLB (Odds Ratio [OR]: 8.28). GBA1 mutation carriers presented a more malignant phenotype, with earlier symptom onset, more severe motor and cognitive dysfunctions, more visual hallucinations and rapid eye movement sleep disorder. GBA1 mutations were associated with "purer" neuropathological DLB. No therapeutic recommendations exist and clinical trials targeting GCase are just starting in DLB patients.

CONCLUSIONS AND RELEVANCE

This review reports a link between GBA1 mutations and the DLB phenotype with limited evidence due to the small number of studies.

摘要

重要性

路易体痴呆症 (DLB) 是一种与磷酸化α-突触核蛋白异常积累相关的神经退行性疾病。GBA1 是编码溶酶体酶葡萄糖脑苷脂酶 (GCase) 的基因，其突变是 DLB 的一个风险因素。

目的

报告所有探索 GBA1 突变与 DLB 之间关联的可用数据。

证据回顾

在 PubMed、Cochrane 和 ClinicalTrials.gov 上，确定了 2003 年至 2022 年期间所有关于人类 GCase 和 DLB 的出版物。

发现

共纳入 29 项研究，证实了 GBA1 突变与 DLB 之间存在强烈关联（优势比 [OR]：8.28）。GBA1 突变携带者表现出更恶性的表型，发病更早，运动和认知功能障碍更严重，更易出现幻视和快速眼动睡眠障碍。GBA1 突变与“更纯粹”的神经病理学 DLB 相关。由于研究数量有限，目前尚无治疗建议，针对 GCase 的临床试验刚刚开始在 DLB 患者中进行。