文摘
摘要目的:评估周边synucleinopathy程度的遗传性帕金森病(PD)。
背景:存款的α-synuclein(α-syn)脑干描述特发性帕金森病(iPD),并且还发现在皮肤自主神经纤维。的程度intra-neuronal synucleinopathy遗传形式的PD一直不太清楚。在这里,我们描述的第一个系列直接比较外围synucleinopathy最常见的遗传PD亚型,LRRK2, GBA,帕金,SNCA, DJ1型。
设计/方法:α-Syn沉积在交感神经元去量化了α-syn-tyrosine羟化酶(TH) C2 colocalization指数从65例颈部皮肤活检。其中包括30名学生与致病性突变SNCA (N = 3),帕金(biallelic (N = 7)或monoallelic [N = 3]), LRRK2 (N = 7), GBA (N = 7),或DJ1型(N = 3);19 iPD的病人;12无关的疾病患者(UD);和4个健康志愿者(高压)。
结果:根据基因型值α-syn-TH colocalization指数变化。Intraneuronalα-syn淀积大于控制(CTRL =高压+ UD)范围内观察到体内基因LRRK2 SNCA和参与者和GBA的大部分(83%)和iPD参与者(95%)。相比之下,没有biallelic帕金参与者高α-syn-TH colocalization指数。增加α-syn沉积在一个无症状的SNCA复制载体而不是纯合子GBA参与者没有PD,表明前驱的外围synucleinopathy可能出现在一些但不是全部遗传形式的PD。体内基因LRRK2 Colocalization指数biallelic患者体内基因LRRK2或二基因的突变和GBA突变体内基因LRRK2类似与单个或GBA突变。
结论:体内基因LRRK2 DJ-1 SNCA的人,或GBA基因型的异常增加α-syn沉积在交感神经去,而那些帕金异常。令人惊讶的是,存在与否的外围synucleinopathy体内基因LRRK2患者或帕金突变是一致的,与变量脑干synucleinopathy等病人尸检系列报道。
披露:Risa Isonaka没有披露。戈尔茨坦已经收到相关出版物的出版版税卫生保健。威廉·朱没有披露。戈尔茨坦已经收到相关出版物的出版版税卫生保健。埃利希博士没有披露。爱丽丝辛德勒没有披露。安吉拉Kokkinis没有披露。莎拉Bandres没有披露。戈尔茨坦已经收到相关出版物的出版版税卫生保健。Gonzalez-Alegre博士已经收到个人薪酬在500 - 4999美元的范围作为顾问引发疗法。 Dr. Gonzalez-Alegre has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai Therapeutics. Dr. Gonzalez-Alegre has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NeuExcell. The institution of Dr. Gonzalez-Alegre has received research support from NIH/NINDS. Dr. Gonzalez-Alegre has received intellectual property interests from a discovery or technology relating to health care. Dr. Lopez has nothing to disclose. The institution of Dr. Sidransky has received research support from mjff. The institution of Dr. Sidransky has received research support from Roche. The institution of Dr. Narendra has received research support from National Institutes of Health.
