Elevated Cerebrospinal Fluid α-Synuclein Seeding Activity Predicts Central Lewy Body Diseases.

IF 2.6 4区 医学 Q2 CLINICAL NEUROLOGY Movement Disorders Clinical Practice Pub Date : 2025-01-16 DOI:10.1002/mdc3.14333
David S Goldstein, Parvez Alam, Patti Sullivan, Courtney Holmes, Janna Gelsomino, Andrew G Hughson, Byron Caughey
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Abstract

Background: Cerebrospinal fluid (CSF) α-synuclein seeding activity (SSA) via a seed amplification assay might predict central Lewy body diseases (LBD) in at-risk individuals.

Objective: The aim was to assess CSF SSA in a prospective, longitudinal study.

Methods: Participants self-reported risk factors were genetics, olfactory dysfunction, dream enactment behavior, orthostatic intolerance, or hypotension; individuals who had ≥3 confirmed risk factors underwent CSF sampling and were followed for up to 7.5 years. Participants who developed a central LBD (LBD+) were compared to those who did not. Quadruplicate SSA areas under the curve (AUC) were averaged.

Results: Of 11 subjects with average AUCs above 500,000 units, 7 (64%) developed a central LBD compared to 1 of 20 (5%), with AUCs below the cutoff value (P = 0.0011 by log-rank test). Conversely, 7 of 8 (88%) LBD+ participants had elevated initial AUCs.

Conclusions: Increased CSF SSA predicts central LBDs. Individuals who develop a central LBD have elevated initial SSA AUCs.

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脑脊液α-突触核蛋白种子活性升高预测中枢路易体疾病。
背景:脑脊液(CSF) α-突触核蛋白种子活性(SSA)通过种子扩增试验可以预测高危人群的中枢路易体病(LBD)。目的:在一项前瞻性、纵向研究中评估脑脊液SSA。方法:参与者自我报告的危险因素包括遗传、嗅觉功能障碍、做梦行为、直立不耐受或低血压;确认有3个以上危险因素的个体接受脑脊液采样,随访时间长达7.5年。出现中枢性LBD (LBD+)的参与者与没有出现的参与者进行比较。取曲线下四次重复SSA面积(AUC)的平均值。结果:在11名平均auc高于500,000单位的受试者中,7名(64%)发生了中枢性LBD,而20名受试者中有1名(5%)发生了中枢性LBD, auc低于临界值(log-rank检验P = 0.0011)。相反,8名LBD+参与者中有7名(88%)初始auc升高。结论:脑脊液SSA升高预示中枢性lbd。发展为中枢性LBD的个体初始SSA auc升高。
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来源期刊
CiteScore
4.00
自引率
7.50%
发文量
218
期刊介绍: Movement Disorders Clinical Practice- is an online-only journal committed to publishing high quality peer reviewed articles related to clinical aspects of movement disorders which broadly include phenomenology (interesting case/case series/rarities), investigative (for e.g- genetics, imaging), translational (phenotype-genotype or other) and treatment aspects (clinical guidelines, diagnostic and treatment algorithms)
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