无症状 LRRK2 突变携带者的多巴胺周转率增加。

Dopamine turnover increases in asymptomatic LRRK2 mutations carriers.

机构信息

Department of Physics and Astronomy, University of British Columbia, Vancouver British Columbia, Canada.

出版信息

Mov Disord. 2010 Dec 15;25(16):2717-23. doi: 10.1002/mds.23356.

PMID:20939082

Abstract

Increase in dopamine (DA) turnover was found to occur early in symptomatic Parkinson's disease (PD) and to be functionally related to the dopamine transporter (DAT). The objectives of this study were to examine changes in DA turnover in the asymptomatic PD phase; to compare them with changes in other dopaminergic markers, and to investigate a possible relationship between DAT and DA turnover. Eight subjects from families at increased risk of PD due to LRRK2 mutation were investigated. Positron emission tomography imaging was performed with: ¹⁸F-fluorodopa to determine the effective DA distribution volume (EDV), the inverse of DA turnover, and the DA uptake rate K(occ), a marker of DA synthesis and storage; ¹¹C-methylphenidate (MP, a DAT marker) and ¹¹C-dihydrotetrabenazine (DTBZ, a VMAT2 marker) to estimate the binding potentials BP(ND_MP) and BP(ND_DTBZ). On average, EDV showed the largest reduction from age-matched control values (42%) followed by BP(ND_MP) (23%) and BP(ND_DTBZ) (17%), whereas K(occ) remained in the normal range for all subjects. No correlation was found between EDV and any other marker. DA turnover was found to be elevated in asymptomatic mutation carriers at increased risk of PD. Such change was determined to be larger than and statistically independent from changes observed with the other markers. These results support a compensatory role of increased DA turnover in presymptomatic disease and indicate that at this stage, in contrast to the symptomatic PD phase, increased turnover is not related to DAT.

摘要

研究发现，多巴胺（DA）周转率在有症状帕金森病（PD）的早期就会增加，并且与多巴胺转运体（DAT）功能相关。本研究的目的是检查无症状 PD 阶段 DA 周转率的变化；将其与其他多巴胺能标志物的变化进行比较，并研究 DAT 与 DA 周转率之间的可能关系。对 8 名由于 LRRK2 突变而处于 PD 高危状态的家族成员进行了研究。使用¹⁸F-氟多巴进行正电子发射断层扫描成像，以确定有效 DA 分布容积（EDV），即 DA 周转率的倒数，以及 DA 摄取率 K（occ），这是 DA 合成和储存的标志物；¹¹C-甲基苯丙胺（MP，DAT 标志物）和¹¹C-二氢四苯并嗪（DTBZ，VMAT2 标志物），以估计 BP（ND_MP）和 BP（ND_DTBZ）。平均而言，EDV 与年龄匹配的对照组相比，降幅最大（42%），其次是 BP（ND_MP）（23%）和 BP（ND_DTBZ）（17%），而 K（occ）在所有受试者中均处于正常范围内。EDV 与任何其他标志物之间均无相关性。在 PD 高危无症状突变携带者中，发现 DA 周转率升高。这种变化被确定比其他标志物观察到的变化更大且具有统计学意义。这些结果支持了在疾病前驱期增加的 DA 周转率的代偿作用，并表明在这个阶段，与有症状的 PD 阶段相反，增加的周转率与 DAT 无关。