Diffusion MRI and α-Synuclein Seed Amplification Status in Parkinson's Disease.

IF 7.7 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology Pub Date : 2026-05-07 DOI:10.1002/ana.78252

Shannon Y Chiu, Wei-En Wang, Robin Chen, Jesse C DeSimone, Derek B Archer, Charles H Adler, Shyamal H Mehta, Sara R Dresler, Melissa J Armstrong, Nikolaus McFarland, Michael Okun, David E Vaillancourt

{"title":"Diffusion MRI and α-Synuclein Seed Amplification Status in Parkinson's Disease.","authors":"Shannon Y Chiu, Wei-En Wang, Robin Chen, Jesse C DeSimone, Derek B Archer, Charles H Adler, Shyamal H Mehta, Sara R Dresler, Melissa J Armstrong, Nikolaus McFarland, Michael Okun, David E Vaillancourt","doi":"10.1002/ana.78252","DOIUrl":null,"url":null,"abstract":"Objective: Positive α-synuclein seed amplification assay (SAA) is a biomarker found in most people with Parkinson's disease (PD). We explored if free-water (FW) imaging detects microstructural differences in the brains of patients with early PD with SAA+ or SAA- status.Methods: We studied patients with PD with baseline diffusion imaging and α-synuclein SAA data from the Parkinson's Progression Markers Initiative (PPMI). We compared FW, FW corrected fractional anisotropy (FAT), and clinical characteristics between SAA+ and SAA- groups. We also applied the Automated Imaging Differentiation for Parkinsonism (AIDP) at baseline to classify PD versus atypical parkinsonism, stratified by SAA status.Results: Among 462 participants (41 SAA- and 421 SAA+), individuals with SAA+ had hyposmia and shorter motor symptom duration before baseline magnetic resonance imaging (MRI). AIDP identified PD in 92.4% (n = 427, 91.6% had SAA+) and classified 7.6% as atypical parkinsonism (n = 35, 85.7% had SAA+). At baseline, SAA+ individuals had lower FW in the superior cerebellar peduncle, compared to SAA- (pFDR < 0.05). No significant differences in FAT were found between groups.Interpretation: Positive α-synuclein SAA was associated with focal microstructural differences but did not distinguish broader diffusion MRI (dMRI) changes across FW and FAT metrics. These findings indicate that molecular confirmation of synuclein aggregation (via SAA) provides limited stratification of neurodegeneration detected by FW imaging in early PD. ANN NEUROL 2026.","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7000,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/ana.78252","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objective: Positive α-synuclein seed amplification assay (SAA) is a biomarker found in most people with Parkinson's disease (PD). We explored if free-water (FW) imaging detects microstructural differences in the brains of patients with early PD with SAA+ or SAA- status.

Methods: We studied patients with PD with baseline diffusion imaging and α-synuclein SAA data from the Parkinson's Progression Markers Initiative (PPMI). We compared FW, FW corrected fractional anisotropy (FA_T), and clinical characteristics between SAA+ and SAA- groups. We also applied the Automated Imaging Differentiation for Parkinsonism (AIDP) at baseline to classify PD versus atypical parkinsonism, stratified by SAA status.

Results: Among 462 participants (41 SAA- and 421 SAA+), individuals with SAA+ had hyposmia and shorter motor symptom duration before baseline magnetic resonance imaging (MRI). AIDP identified PD in 92.4% (n = 427, 91.6% had SAA+) and classified 7.6% as atypical parkinsonism (n = 35, 85.7% had SAA+). At baseline, SAA+ individuals had lower FW in the superior cerebellar peduncle, compared to SAA- (pFDR < 0.05). No significant differences in FA_T were found between groups.

Interpretation: Positive α-synuclein SAA was associated with focal microstructural differences but did not distinguish broader diffusion MRI (dMRI) changes across FW and FA_T metrics. These findings indicate that molecular confirmation of synuclein aggregation (via SAA) provides limited stratification of neurodegeneration detected by FW imaging in early PD. ANN NEUROL 2026.

查看原文本刊更多论文

扩散MRI与α-突触核蛋白种子扩增在帕金森病中的地位。

目的：α-突触核蛋白种子扩增阳性检测（SAA）是大多数帕金森病（PD）患者的生物标志物。我们探讨了自由水（FW）成像是否能检测SAA+或SAA-状态的早期PD患者的大脑微观结构差异。方法：我们研究PD患者的基线扩散成像和帕金森进展标志物倡议（PPMI）的α-突触核蛋白SAA数据。我们比较了SAA+组和SAA-组的FW、FW校正分数各向异性（FAT）和临床特征。我们还在基线时应用帕金森病自动成像鉴别（AIDP）对帕金森病和非典型帕金森病进行分类，按SAA状态分层。结果：在462名参与者中（41名SAA-和421名SAA+）， SAA+的个体在基线磁共振成像（MRI）前出现低氧和较短的运动症状持续时间。AIDP诊断PD的比例为92.4% (n = 427， SAA+的比例为91.6%)，非典型帕金森的比例为7.6% （n = 35， SAA+的比例为85.7%）。在基线时，与SAA-相比，SAA+个体在小脑上脚的FW较低（两组之间发现pFDR T）。解释：α-synuclein SAA阳性与局部显微结构差异有关，但不能区分FW和FAT指标上更广泛的弥散MRI （dMRI）变化。这些结果表明，突触核蛋白聚集的分子确认（通过SAA）为早期PD患者FW成像检测到的神经变性提供了有限的分层。Ann neurol 2026。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.