Toxic tau: structural origins of tau aggregation in Alzheimer's disease

Alzheimer’s disease is characterized by the extracellular accumulation of the amyloidβin the form of amyloid plaques and the intracellular deposition of the microtubule-associated protein tau in the form of neurofibrillary tangles.Most of the Alzheimer’s drugs targeting amyloidβhave been failed in clinical trials.Particularly,tau pathology connects greatly in the pathogenesis of Alzheimer’s disease.Tau protein enhances the stabilization of microtubules that leads to the appropriate function of the neuron.Changes in the quantity or the conformation of tau protein could affect its function as a microtubules stabilizer and some of the processes wherein it is involved.The molecular mechanisms leading to the accumulation of tau are principally signified by numerous posttranslational modifications that change its conformation and structural state.Therefore,aberrant phosphorylation,as well as truncation of tau protein,has come into focus as significant mechanisms that make tau protein in a pathological entity.Furthermore,the shape-shifting nature of tau advocates to comprehend the progression of Alzheimer’s disease precisely.In this review,we emphasize the recent studies about the toxic and shape-shifting nature of tau in the pathogenesis of Alzheimer’s disease.     

复方丹参滴丸对老年冠心病患者血流变学、血脂及炎性反应递质的影响

目的：探究复方丹参滴丸对老年冠心病患者血流变学、血脂及炎性反应递质的影响。方法：选取2015年1月至2017年12月海南省人民医院收治的老年冠心病患者154例作为研究对象，按照随机数字表法随机分为对照组和观察组，每组77例。对照组采用常规西药治疗，观察组在此基础上加服复方丹参滴丸。比较治疗前后2组患者的血流变学、血脂、炎性反应递质和疗效。结果：观察组治疗有效率为92.21%，明显高于对照组治疗有效率79.22%，差异有统计学意义（P<0.05）。治疗后，2组总胆固醇（TC）、三酰甘油（TG）和低密度脂蛋白（LDL）水平均升高，差异有统计学意义（P<0.05），且观察组高于对照组，2组差异有统计学意义（P<0.05）。2组血流变学指标、高密度脂蛋白（HDL）、IL-6和TNF-α水平治疗后均降低（P<0.05），且观察组降低更明显，差异有统计学意义（P<0.05）。结论：复方丹参滴丸联合常规西药治疗冠心病患者，能够调节脂代谢，降低炎性反应，改善血流变学。     

The effect of Origanum majorana tea on motor and non-motor symptoms in patients with idiopathic Parkinson's disease: A randomized controlled pilot study

AimsThe effect of Origanum majorana tea consumption on motor and non-motor symptoms was investigated in patients with idiopathic Parkinson's disease, measured by validated tools.MethodsSixty patients with idiopathic Parkinson's disease and under conventional medication were enrolled voluntarily in the study. All participants were randomized on double-blind to placebo or Origanum majorana. Clinical assessment with validated tools (UPDRSIII, NMSS, and BDI) was done before Origanum majorana or placebo consumption (Day 0) and at the end of the experiment (Day 30).ResultsThe treatment groups were similar at baseline on demographic and clinical variables. During the course of study, nine participants withdrew for reasons of noncompliance and inability to follow-up. Fifty-one participants completed the study. Upon completion of 30 days of treatment, Origanum majorana tea consumption did not decrease the UPDRSIII score ([UPDRSIII^] D0 = 18.76 ± 8.58, D30 = 16.52 ± 7.96, p = 0.069) at the p value was 0.07. However, a statistically significant improvement was noted in NMSS and BDI scores (p < 0.0001 and p < 0.0001, respectively). Assessment of the UPDRSIII, NMSS and BDI scores of the patients did not reflect any improvement with placebo. No side effect was detected during the study^.ConclusionThese findings show improvement of depressive and non-motor signs in patients with Parkinson's disease in the group that consumed Origanum majorana tea in combination with conventional therapy. Improvement of motor signs may need an extended treatment period. However, more research with a large number of participants and lasting longer than 1 month is needed to argue these findings.     

Event-related potential changes due to early-onset Parkinson’s disease in parkin (PARK2) gene mutation carriers and non-carriers

ObjectiveTo investigate cognitive functions in non-demented patients with early-onset Parkinson's disease (PD), and to compare PARK2 gene mutation carriers and non-carriers by means of event-related brain potentials (ERPs).MethodsThe participants comprised patients with early-onset PD (EOPD) and healthy controls (HC). Patients with EOPD were divided into two groups as carriers of known pathogenic variants of PARK2 gene (EOPD-PC) and non-carriers of genes involved in familial PD (EOPD-NC). ERP data were collected during auditory oddball and visual continuous performance test (CPT).ResultsBoth EOPD groups (EOPD-PC and EOPD-NC) displayed reduced and delayed P3 in response to oddball target and CPT NoGo. CPT Go P3 was reduced in EOPD-NC but not in EOPD-PC. Oddball target N1 was reduced and P2 was enhanced in both EOPD-PC and EOPD-NC. In both cognitive tasks, RTs were prolonged and accuracy was lower in EOPD-PC and EOPD-NC.ConclusionsWe found several EOPD-related neurophysiologic changes, implying impairments in cognitive functions. Pairwise comparisons between EOPD-PC and EOPD-NC revealed no significant ERP marker.SignificanceIn this study, the confounding effect of normative aging was somewhat excluded compared with many previous studies. In contrast with the many oddball studies in non-demented PD, we clearly observed reduced and prolonged P3 in early-onset PD. Our NoGo P3 findings also contribute to the limited ERP research concerning response inhibition.     

Localization of motor and verbal fluency effects in subthalamic DBS for Parkinson's disease

IntroductionSubthalamic nucleus deep brain stimulation (STN DBS) improves cardinal motor symptoms of Parkinson's disease (PD) but can worsen verbal fluency (VF). An optimal site of stimulation for overall motor improvement has been previously identified using an atlas-independent, fully individualized, field-modeling approach. This study examines if cardinal motor components (bradykinesia, tremor, and rigidity) share this identified optimal improvement site and if there is co-localization with a site that worsens VF.MethodsAn atlas-independent, field-modeling approach was used to identify sites of maximal STN DBS effect on overall and cardinal motor symptoms and VF in 60 patients. Anatomic coordinates were referenced to the STN midpoint. Symptom severity was assessed with the MDS-UPDRS part III and established VF scales.ResultsSites for improved bradykinesia and rigidity co-localized with each other and the overall part III site (0.09 mm lateral, 0.93 mm posterior, 1.75 mm dorsal). The optimal site for tremor was posterior to this site (0.10 mm lateral, 1.40 mm posterior, 1.93 mm dorsal). Semantic and phonemic VF sites were indistinguishable and co-localized medial to the motor sites (0.32 mm medial, 1.18 mm posterior, 1.74 mm dorsal).ConclusionThis study identifies statistically distinct, maximally effective stimulation sites for tremor improvement, VF worsening, and overall and other cardinal motor improvements in STN DBS. Current electrode sizes and voltage settings stimulate all of these sites simultaneously. However, future targeted lead placement and focused directional stimulation may avoid VF worsening while maintaining motor improvements in STN DBS.