脑脊液生物标志物在早期帕金森病诊断中的应用

目的探讨脑脊液生物标志物在早期帕金森病(Parkinson’s disease,PD)诊断中的临床应用价值。方法选取PD患者170例,依据H-Y评分分为早期组(90例)、中期组(60例)和晚期组(20例);另选取健康志愿者30例为对照组。采集所有受试者脑脊液标本,免疫比浊法检测β-内啡肽(β-EP)及亮氨酸-脑啡肽(LEK),酶联免疫吸附法检测α-突触核蛋白(α-syn),并进行组间比较。同时,分析H-Y评分与β-EP、LEK及α-syn水平的相关性。结果早、中、晚期3组PD患者脑脊液中β-EP水平分别为(42.74±2.37)pg/mL、(39.12±3.92)pg/mL、(36.64±3.86)pg/mL,而LEK水平分别为(91.57±4.25)、(92.26±5.04)、(92.37±5.41)ng/L;PD患者脑脊液中β-EP水平显著低于对照组[(46.21±1.37)pg/mL],而LEK水平显著高于对照组[(86.05±2.58) ng/L],差异均有统计学意义(P0.05)。PD患者脑脊液α-syn水平显著低于对照组,差异有统计学意义(P0.05)。PD患者脑脊液中β-EP、α-syn水平与疾病分期具有相关性(r=-0.632,-0.742,P0.05)。结论通过检测脑脊液中β-EP、α-syn水平有助于早期诊断PD并评估病情。     

外周组织中α-突触核蛋白作为帕金森病生物标志物的研究进展

帕金森病(PD)是以黑质多巴胺能神经元变性丢失和路易小体形成为特征的神经系统退行性疾病,由于缺乏特异性生物标志物,其早期诊断准确率受限.α-突触核蛋白(α-syn)是构成路易小体的关键蛋白,α-syn不仅存在于中脑多巴胺能神经元,还在皮肤、唾液腺等外周组织中广泛分布,并且外周神经系统α-syn病理改变可能早于中枢神经系...     

帕金森病组织和体液中α-突触核蛋白检测进展

帕金森病(PD)是一种中枢神经系统退行性疾病,其流行度及产生的社会经济负担仅次于阿尔茨海默病(AD)。PD以静止性震颤、肌强直、运动迟缓和姿势平衡障碍等为主要临床表现;病理特征为路易小体(LB),即黑质致密部的多巴胺能神经元大量变性丢失、残存的神经元胞质内出现的嗜酸性包涵体。PD诊断主要依据长期临床观察及对左旋多巴治疗是否敏感,但容易漏诊和误诊。PD确定诊断只能依据死亡后的尸检病理结果,尚无特异敏感的生化指标可作为确诊的依据。研究人员就PD生物学标志物进行了不同形式、不同规模的研究,以期探寻一种理想的PD生物学标志物,望其兼具灵敏度高、特异性强、微创甚至无创、可重复等特点,为PD早期诊断、与其他疾病鉴别、掌控疾病进程、评估疗效提供确切依据。当前PD的生物化学标志物研究涉及临床前期症状、生物化学、影像学及基因学多个方面,近年来对于α-突触核蛋白的研究相对深入。     

基因突变与α-突触核蛋白在帕金森病的研究进展

帕金森病( Parkinson' s disease,PD)是目前世界第二大神经退行性疾病.PD是由黑质致密部的多巴胺能神经元大量丢失和α-突触核蛋白(α-synuclein,α-syn)聚集形成路易小体( Lewy Body,LBS)和路易神经纤维( Lewy Neurites)为特征的病变[1].Spillanti...     

基因突变与α-突触核蛋白在帕金森病的研究进展

帕金森病(Parkinson's disease,PD)是目前世界第二大神经退行性疾病.PD是由黑质致密部的多巴胺能神经元大量丢失和α-突触核蛋白(α-synuclein,oα-syn)聚集形成路易小体(Lewy Body,LBS)和路易神经纤维(Lewy Neurites)为特征的病变[1].Spillantini等...     

肠道菌群与帕金森病的相关性研究进展

<正>帕金森病(Parkinson disease,PD)又称震颤麻痹,是一种慢性神经系统退行性疾病,以黑质多巴胺能神经元变性、缺失、减少,神经元α-突触核蛋白沉积及路易小体形成为病理特征。临床表现包括震颤、肌强直、动作迟缓、姿势平衡障碍的运动症状及胃肠功能紊乱、睡眠行为异常和抑郁等非运动症状[1]。目前PD的发病机制尚不完全明确,     

α-突触核蛋白及其在帕金森病发病中的可能机制

α-突触核蛋白（AS）足Lewy体的重要组成成分。AS基因定位于第4号染色体，其突变型与常染色体显性遗传性帕金森病（PD）的发病密切相关。在PD中，AS出现了折叠错误和排列混乱。AS的聚集能力，特别是在氧化应激状态下，被认为是其病理机制的核心，AS的异常聚集和降解障碍导致蛋白酶的抑制和多巴胺能神经元的死亡。因此，AS致病形式对认识PD的发生有重要意义。     

脑脊液 α-突触核蛋白和SWI在早期帕金森病诊断中的价值

目的探讨脑脊液α-突触核蛋白测定和SWI在早期帕金森病(Parkinson’s disease,PD)诊断中的价值。方法收集郑州大学第一附属医院2015-08—2017-12确诊的PD患者,根据H-Y分级分为早期PD组和中晚期PD组,招募同一时期内年龄及性别与PD组相匹配的健康志愿者,采用酶联免疫吸附测定试剂盒检测脑脊液α-突触核蛋白,所有患者及对照组同时行头颅横断位T_1WI、T_2WI和SWI成像检查。结果 PD组脑脊液中α-突触核蛋白水平低于对照组;不同分期PD比较,中晚期PD组脑脊液中α-突触核蛋白水平低于早期PD组,差异有统计学意义(P0.01)。头颅SWI分析显示,PD组与对照组的脑铁沉积比较,在苍白球、尾状核头和黑质区差异有统计学意义(P0.05),早期PD组与中晚期PD组在相同部位铁沉积比较,差异无统计学意义(P0.05);在红核和壳核区域,PD组与对照组铁沉积比较,差异无统计学意义(P0.05),早期PD组与中晚期PD组铁沉积比较,差异无统计学意义(P0.05)。结论脑脊液α-突触核蛋白是PD早期病理改变的重要生物学指标。SWI通过检测脑内异常铁沉积,可用于协同诊断PD。     

帕金森病的免疫治疗研究进展

帕金森病的发病机制尚不完全清楚,目前还没有根本有效的药物治疗。近年来免疫治疗在帕金森疾病的治疗方面显示出良好的前景。免疫治疗主要通过三个方面:一是α-突触核蛋白抗体的被动免疫治疗;二是依赖T淋巴细胞的疫苗免疫治疗;三是核酸疫苗主动免疫治疗。     

α-突触核蛋白过表达转基因帕金森病动物模型研究进展

帕金森病是最常见的神经变性疾病之一。帕金森病动物模型是解释疾病病因学根本机制,开发新的神经保护药物和治疗策略研究的必不可少的工具。该文综述了目前常用的几类帕金森病α-突触核蛋白过表达转基因动物模型及其优缺点。转基因动物模型是目前最为重要的帕金森病动物模型;较全面地反映帕金森病病因及发病机理、病理特点,将是帕金森病动物模型研究新时代的开始,也是今后研究探讨的方向。     

Neuroimaging in Parkinson's disease: from pathology to diagnosis

Imaging allows a window into the pathology of PD during life, and potentially even prior to the appearance of motor manifestations. Functional imaging using dopaminergic tracers with either PET or SPECT can identify dopamine deficiency but may not reliably differentiate between PD and other akinetic-rigid disorders. On the other hand, dopaminergic tracer imaging can identify pre-motor changes in subjects at high risk of developing PD and may be useful as a biomarker to assess disease progression, with caveats. Glucose or cerebral blood flow imaging can provide complementary information on patterns of cerebral activation and thereby be useful for diagnosis and for the assessment of compensatory strategies. Although traditionally considered to be of limited utility for the study of PD and related disorders, novel magnetic resonance imaging techniques are showing increasing promise for diagnosis and potentially as biomarkers. These applications will be reviewed here, as will the potential use of imaging to assess Braak's hypothesis of caudal to rostral degeneration in vivo.     

Amygdala pathology in Parkinson's disease

The amygdala undergoes severe pathological changes during the course of Parkinson's disease (PD). Lewy bodies and Lewy neurites are distributed in a specific manner throughout the nuclear complex. The lesional pattern displays only minor interindividual variation. The most prominent changes occur in the accessory cortical and central nuclei. The cortical, accessory basal and granular nuclei show less severe alterations, while the basal and lateral nuclei, as well as the intercalated cell masses, generally remain uninvolved. The amygdala receives a broad range of afferents, allowing integration of exteroceptive information with interoceptive data. It generates major projections to the isocortex (the prefrontal cortex in particular), limbic system (hippocampus and entorhinal region) and centers regulating endocrine and autonomic functions. The specific lesional pattern seen in PD destroys part of the nuclear gray matter and its connections and, thus, may likely contribute to the development of behavioral changes and autonomic dysfunction.     

Caudate nucleus pathology in Parkinson's disease: ultrastructural and biochemical findings in biopsy material

Summary Ultrastructural and biochemical properties of caudate nucleus (CN) biopsies in two patients with advanced Parkinson's disease (PD) were compared with three CN specimens removed during surgery for intracranial tumors. An additional two specimens from neurologically intact patients (59 and 86 years old) were removed during autopsy (performed 3 and 4 h post mortem, respectively) for electron microscopic studies. Dopamine levels in PD were reduced to less than 15% of control values. Both PD patients showed frequent dystrophic neurites and transsynaptic degeneration of neurons and neuritic processes. These changes were not found in CN from the four control individuals. Only a few dystrophic neurites were noticed in one 67-year-old control patient. The development of neuroaxonal dystrophy in CN is consistent with a dying-back process, probably accompanying abnormalities of axonal transport in PD. Transsynaptic degeneration of neurons in CN very likely represents a morphological marker of disease severity. The occurrence of this change may account for the poor clinical response of patients with advanced PD to intracerebral implantation of dopaminergic tissues.Presented at XIth International Congress of Neuropathology Kyoto, Japan September 2–8, 1990     

Increased periodontal pathology in Parkinson's disease

Parkinson's disease is characterized by rigidity, akinesia and tremor, all of which interfere with automated small hand movements potentially affecting oral care. In addition, medication and craving for sweets are other risk factors for dental and periodontal disease in these patients. Here, we report the Community Periodontal Index for Treatment Needs (CPITN) data in 70 patients with Parkinson's disease and 85 age-matched control subjects. CPITN indices were assessed in all 6 sextants. Mean CPITN indices of control subjects ranged from 1.6 +/- 0.2 in the upper frontal sextant to 2.5 +/- 0.2 in the upper left lateral sextant. 17.9% of controls showed severely affected teeth (CPITN code 4) in the upper left or upper right sextant, while there were no teeth at risk in the upper frontal sextant. Patients suffering from Parkinson's disease, however, had a markedly increased mean CPITN index in the upper frontal sextant (2.4 +/- 0.2) with 11.5 patients having severely affected teeth (CPITN code 4). CPITN indices in all other sextants were less severely increased. Overall, there was a significant difference between mean CPITN indices of patients and controls (p < 0.05). It seems also noteworthy that female controls had lower CPITN indices in all sextants compared with male controls. This gender difference, however, was reversed in Parkinson's patients. We believe that problems in oral hygiene contribute to this increased periodontal pathology in patients with Parkinson's disease, which may further compromise the quality of life.     

Recent developments in the pathology of Parkinson's disease

Parkinson's disease (PD) is morphologically characterized by progressive loss of neurons in the substantia nigra pars compacta (SNpc) and other subcortical nuclei associated with intracytoplasmic Lewy bodies and dystrophic (Lewy) neurites mainly in subcortical nuclei and hippocampus und, less frequently in cerebral cortex. SN cell loss is significantly related to striatal dopamine (DA) deficiency as well as to both the duration and clinical severity of disease, The two major clinical subtypes of PD show different morphologic lesion patterns: the akinetic-rigid form has more severe cell loss in the ventrolateral part of SN with negative correlation to DA loss in the posterior putamen, and motor symptoms related to overacitivty of the GABAergic "indirect" motor loop, which causes inhibition of the glutamatergic thalamocortical pathway and reduced cortical activation. The tremor-dominant type shows more severe cell loss in the medial SNpc and retrorubal field A 8, which project to the matrix of the dorsolateral striatum and ventromedial thalamus, thus causing hyperactivity of thalamomotor and cerebellar projections. These and experimental data suggesting different pathophysiological mechanisms for the major clinical subtypes of PD may have important therapeutic implications. Lewy bodies, the morphologic markers of PD, are composed of hyperphosphorylated neurofilament proteins, lipids, redox-active iron, ubiquitin, and alpha-synuclein, showing a continuous accumulation in the periphery and of ubiquitin in the central core. Alpha-synuclein, is usually unfolded in alpha-helical form. By gene mutation, environmental stress or other factors it can be transformed to beta-folding which is sensible to self-aggregation in filamentous fibrils and formation of insoluble intracellular inclusions that may lead to functional disturbances and, finally, to death of involved neurons. While experimental and tissue culture studies suggest that apoptosis, a genetically determined form of programmed cell death, represents the most common pathway in neurodegeneration, DNA fragmentation, overexpression of proapoptotic proteins and activated caspase-3, the effector enzyme of the terminal apopoptic cascade, have only extremely rarely been detected in SN of PD brains. This is in accordance with the rapid course of apoptotis and the extremely slow progression of the neurodegenerative process in PD. The biological role of Lewy bodies and other intracellular inclusions, the mechanisms of the intracellular aggregation of insoluble protein deposits, and their implication for cellular dysfunction resulting in neurodegeneration and cell demise are still unresolved. Further elucidation of the basic molecular mechanisms of cytoskeletal lesions will provide better insight into the pathogenesis of neurodegeneration in PD and related disorders.     

The cellular pathology of Parkinson's disease

Parkinson's disease (PD) is a common neurodegenerative disorder of unknown cause that occurs in adults. The presence of Lewy bodies (LB) in association with nerve cell loss in the substantia nigra and various other regions of the nervous system is a diagnostic hallmark of the disease. In 1997, a mutation was identified in the α‐synuclein gene in families with autosomal dominant PD. Subsequent immunohistochemical studies have revealed that all of the LB in familial and sporadic PD contain the gene product α‐synuclein: abnormal filaments that constitute LB were clearly recognized by antibodies against α‐synuclein. Moreover, it was shown that the glial cells, both astrocytes and oligodendrocytes, are also affected by α‐synuclein pathology. Recently, a novel protein, synphilin‐1, has been identified that interacts with α‐synuclein. Interestingly, synphilin‐1 immunohistochemistry has demonstrated that this protein is present in the central core of classical (brainstem) LB, which are composed mainly of densely packed vesicular structures. The role of both α‐synuclein and synphilin‐1 in normal conditions has yet to be clarified.