■皮肤磷酸化α-突触核蛋白(p-α-syn)沉积是特发性帕金森病(iPD)的重要生物标志物。最近的研究已经报道了具有共同遗传形式的PD的患者的突触核蛋白病。
■本研究旨在检测CHCHD2或RAB39B突变的罕见遗传性PD患者的p-α-syn沉积特征。此外,这项研究还旨在描述遗传性PD患者的外周α-突触核蛋白朊病毒样活性,并获得遗传性PD的皮肤突触核蛋白病特征是否与中枢神经病理学一致。
■我们从161名参与者的远端腿(DL)和近端颈部(C7)进行了四次皮肤活检样本,包括四名CHCHD2突变的患者,两名RAB39B突变患者,16例PRKN突变患者,14例LRRK2突变患者,五名GBA突变患者,100例IPD患者,和20个健康对照。我们使用免疫荧光染色和接种扩增测定(SAA)检测了皮肤突触核蛋白病。还进行了系统的文献综述,涉及64例皮肤活检和205例遗传性PD患者的尸检。
■P-α-syn在CHCHD2,LRRK2或GBA突变的PD患者的外周皮肤神经中沉积,但在RAB39B或PRKN突变的患者中没有沉积。遗传性PD和iPD患者之间的α-syn阳性沉积物的位置或比率没有显着差异。周围皮肤突触核蛋白病似乎很好地代表了遗传性PD的脑突触核蛋白病,尤其是常染色体显性遗传PD(AD-PD)。iPD和LRRK2和GBA突变患者的皮肤α-突触核蛋白SAA分析显示有朊病毒样活性。
■外周皮神经中的P-α-syn沉积,使用SAA和免疫荧光染色检测,将来可能会成为遗传PD和iPD的准确生物标志物。
UNASSIGNED: Cutaneous phosphorylated alpha-synuclein (p-α-syn) deposition is an important biomarker of idiopathic Parkinson\'s disease (iPD). Recent studies have reported synucleinopathies in patients with common genetic forms of PD.
UNASSIGNED: This study aimed to detect p-α-syn deposition characteristic in rare genetic PD patients with CHCHD2 or RAB39B mutations. Moreover, this study also aimed to describe peripheral alpha-synuclein prion-like activity in genetic PD patients, and acquire whether the cutaneous synucleinopathy characteristics of genetic PD are consistent with central neuropathologies.
UNASSIGNED: We performed four skin biopsy samples from the distal leg (DL) and proximal neck (C7) of 161 participants, including four patients with CHCHD2 mutations, two patients with RAB39B mutations, 16 patients with PRKN mutations, 14 patients with LRRK2 mutations, five patients with GBA mutations, 100 iPD patients, and 20 healthy controls. We detected cutaneous synucleinopathies using immunofluorescence staining and a seeding amplification assay (SAA). A systematic literature review was also conducted, involving 64 skin biopsies and 205 autopsies of genetic PD patients with synucleinopathy.
UNASSIGNED: P-α-syn was deposited in the peripheral cutaneous nerves of PD patients with CHCHD2, LRRK2, or GBA mutations but not in those with RAB39B or PRKN mutations. There were no significant differences in the location or rate of α-syn-positive deposits between genetic PD and iPD patients. Peripheral cutaneous synucleinopathy appears to well represent brain synucleinopathy of genetic PD, especially autosomal dominant PD (AD-PD). Cutaneous α-synuclein SAA analysis of iPD and LRRK2 and GBA mutation patients revealed prion-like activity.
UNASSIGNED: P-α-syn deposition in peripheral cutaneous nerves, detected using SAA and immunofluorescence staining, may serve as an accurate biomarker for genetic PD and iPD in the future.