Spinocerebellar ataxia type 11 (SCA11): An update.

Spinocerebellar ataxias, also called autosomal dominant cerebellar ataxias, are a group of neurological genetic diseases characterised by chronic, progressive cerebellar ataxia. The clinical hallmark of spinocerebellar ataxia is the loss of balance and coordination, accompanied by slurred speech. Spinocerebellar ataxia type 11 is a rare subtype of spinocerebellar ataxia caused by mutations in the tau tubulin kinase 2 gene. Patients with spinocerebellar ataxia are clinically characterised by slowly progressive cerebellar ataxia, trunk and limb ataxia, and eye movement abnormalities with occasional pyramidal features. Peripheral neuropathy and dystonia are rare. According to the literature, only nine families affected with spinocerebellar ataxia have been reported worldwide. Herein, a series of spinocerebellar ataxia cases are discussed in detail to determine the potential research direction of this dysfunction, including its epidemiology, clinical features, genetic characteristics, diagnosis and differential diagnosis, pathogenic mechanisms, treatment, prognosis, follow-up, genetic counselling and future perspectives, and to improve the overall understanding of spinocerebellar ataxia among clinicians, researchers and patients.

Age and Sex Affect Essential Tremor (ET) Plus: Clinical Heterogeneity in ET Based on the National Survey in China.

The new term essential tremor (ET) plus was proposed in the 2018 tremor consensus criteria. The National Survey of Essential Tremor Plus in China, a large multicenter registry study, aimed to evaluate the clinical features of pure ET and ET plus and explore possible factors related to ET plus. All patients with ET underwent neurological examination and neuropsychological assessment at 17 clinical sites. The diagnosis was made according to the 2018 consensus criteria. Clinicodemographic characteristics were analyzed. A total of 1160 patients were included, including 546 patients with pure ET and 614 patients with ET plus. The proportion of females was significantly higher in the ET plus than that in the pure ET (P = 0.001). The age at onset (AAO) of pure ET showed a bimodal distribution, with peaks in the 2nd and 5th decades. However, the AAO of the ET plus group demonstrated a skewed distribution, with a single peak in the 6th decade. Female sex (OR=1.645, P<0.001), older age (OR=1.023, P<0.001), lower educational level (OR=0.934, P<0.001), head tremor (OR=1.457, P<0.001), and higher the Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS)-II scores (OR=1.134, P<0.001) were significantly associated with ET plus. Old age and female sex may contribute to ET plus development. Pure ET showed a bimodal distribution for AAO, whereas ET plus showed a unimodal distribution. It remains unclear whether pure ET and ET plus are merely different stages of a single disease or represent distinct disease entities.

Characteristics of fatigue in Parkinson's disease: A longitudinal cohort study.

Objective: To assess the prevalence, evolution, clinical characteristics, correlates and predictors of fatigue as well as to investigate the influence of comorbid fatigue on the longitudinal changes in motor and non-motor symptoms over a 2-year longitudinal follow-up period in a large cohort of patients with Parkinson's disease (PD). Materials and methods: A total of 2,100 PD patients were enrolled from the Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC), and their motor and non-motor symptoms were assessed biennially using comprehensive scales, including the 16-item Parkinson Fatigue Scale (PFS-16). Each PD patient was categorized as PD with or without fatigue on the basis of a cut-off mean PFS-16 score of 3.3. Results: The prevalence of fatigue in our cohort was 36.8%. Compared to PD patients without fatigue, PD patients with fatigue were more likely to be older, have a longer disease duration, and higher baseline levodopa equivalent daily dose (all p < 0.05). Moreover, PD patients with fatigue showed more severe motor and non-motor phenotypes than those without fatigue. Overall, high total Unified Parkinson's Disease Rating Scale (UPDRS) score (odds ratio [OR] = 1.016, 95% confidence interval [CI]: 1.009-1.024), Non-Motor Symptoms Scale score (OR = 1.022, 95% CI: 1.015-1.029), postural instability and gait difficulty (PIGD) subtype (OR = 1.586, 95% CI: 1.211-2.079), presence of excessive daytime sleepiness (EDS; OR = 1.343, 95% CI: 1.083-1.666), and wearing-off (OR = 1.282, 95% CI: 1.023-1.607) were significantly associated with fatigue in PD patients (all p < 0.05). High total UPDRS score at baseline (OR = 1.014, 95% CI: 1.002-1.027, p = 0.028) increased the risk of developing fatigue during follow-up. Although significant, the odds ratios were low and confidence intervals were narrow. Analysis of disease progression showed significant group differences in motor and non-motor symptoms. In comparison with the never-fatigue group, the persistent-fatigue group showed significantly greater progression in motor, autonomic dysfunction, sleep, depression and cognitive symptoms (all p < 0.05). Conclusion: Increased disease severity, presence of the PIGD subtype, EDS, and wearing-off were associated with fatigue in PD patients. Significant subgroup-level differences were observed in the progression of motor and non-motor symptoms across different fatigue subgroups of PD patients.

Genome-wide association study using whole-genome sequencing identifies risk loci for Parkinson's disease in Chinese population.

Genome-wide association studies (GWASs) have identified numerous susceptibility loci for Parkinson's disease (PD), but its genetic architecture remains underexplored in populations of non-European ancestry. To identify genetic variants associated with PD in the Chinese population, we performed a GWAS using whole-genome sequencing (WGS) in 1,972 cases and 2,478 controls, and a replication study in a total of 8209 cases and 9454 controls. We identified one new risk variant rs61204179 (Pcombined = 1.47 × 10-9) with low allele frequency, four previously reported risk variants (NUCKS1/RAB29-rs11557080, SNCA-rs356182, FYN-rs997368, and VPS13C-rs2251086), as well as three risk variants in LRRK2 coding region (A419V, R1628P, and G2385R) with genome-wide significance (P < 5 × 10-8) for PD in Chinese population. Moreover, of the reported genome-wide significant risk variants found mostly in European ancestry populations, the correlation coefficient (rb) of effect size accounting for sampling errors was 0.91 between datasets and 63.6% attained P < 0.05 in Chinese population. Accordingly, we estimated a heritability of 0.14-0.18 for PD, and a moderate genetic correlation between European ancestry and Chinese populations (rg = 0.47, se = 0.21). Polygenic risk score (PRS) analysis revealed that individuals with PRS values in the highest quartile had a 3.9-fold higher risk of developing PD than the lowest quartile. In conclusion, the present GWAS identified PD-associated variants in Chinese population, as well as genetic factors shared among distant populations. Our findings shed light on the genetic homogeneity and heterogeneity of PD in different ethnic groups and suggested WGS might continue to improve our understanding of the genetic architecture of PD.

Subtyping of early-onset Parkinson's disease using cluster analysis: A large cohort study.

Background: Increasing evidence suggests that early-onset Parkinson's disease (EOPD) is heterogeneous in its clinical presentation and progression. Defining subtypes of EOPD is needed to better understand underlying mechanisms, predict disease course, and eventually design more efficient personalized management strategies. Objective: To identify clinical subtypes of EOPD, assess the clinical characteristics of each EOPD subtype, and compare the progression between EOPD subtypes. Materials and methods: A total of 1,217 patients were enrolled from a large EOPD cohort of the Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) between January 2017 and September 2021. A comprehensive spectrum of motor and non-motor features were assessed at baseline. Cluster analysis was performed using data on demographics, motor symptoms and signs, and other non-motor manifestations. In 454 out of total patients were reassessed after a mean follow-up time of 1.5 years to compare progression between different subtypes. Results: Three subtypes were defined: mild motor and non-motor dysfunction/slow progression, intermediate and severe motor and non-motor dysfunction/malignant. Compared to patients with mild subtype, patients with the severe subtype were more likely to have rapid eye movement sleep behavior disorder, wearing-off, and dyskinesia, after adjusting for age and disease duration at baseline, and showed a more rapid progression in Unified Parkinson's Disease Rating Scale (UPDRS) total score (P = 0.002), UPDRS part II (P = 0.014), and III (P = 0.001) scores, Hoehn and Yahr stage (P = 0.001), and Parkinson's disease questionnaire-39 item version score (P = 0.012) at prospective follow-up. Conclusion: We identified three different clinical subtypes (mild, intermediate, and severe) using cluster analysis in a large EOPD cohort for the first time, which is important for tailoring therapy to individuals with EOPD.

Sensitivity of Sniffer Dogs for a Diagnosis of Parkinson's Disease: A Diagnostic Accuracy Study.

BACKGROUND: The diagnostic criteria for Parkinson's disease (PD) remain complex, which is especially problematic for nonmovement disorder experts. A test is required to establish a diagnosis of PD with improved accuracy and reproducibility. OBJECTIVE: The study aimed to investigate the sensitivity and specificity of tests using sniffer dogs to diagnose PD. METHODS: A prospective, diagnostic case-control study was conducted in four tertiary medical centers in China to evaluate the accuracy of sniffer dogs to distinguish between 109 clinically established medicated patients with PD, 654 subjects without PD, 37 drug-naïve patients with PD, and 185 non-PD controls. The primary outcomes were sensitivity and specificity of sniffer dog's identification. RESULTS: In the study with patients who were medicated, when two or all three sniffer dogs yielded positive detection results in a sample tested, the index test sensitivity, specificity, and positive and negative likelihood ratios were 91% (95% CI: 84%-96%), 95% (95% CI: 93%-97%), and 19.16 (95% CI: 13.52-27.16) and 0.10 (95% CI: 0.05-0.17), respectively. The corresponding sensitivity, specificity, and positive and negative likelihood ratios in patients who were drug-naïve were 89% (95% CI: 75%-96%), 86% (95% CI: 81%-91%), and 6.6 (95% CI: 4.51-9.66) and 0.13 (95% CI: 0.05-0.32), respectively. CONCLUSIONS: Tests using sniffer dogs may be a useful, noninvasive, fast, and cost-effective method to identify patients with PD in community screening and health prevention checkups as well as in neurological practice. © 2022 International Parkinson and Movement Disorder Society.

The Chinese Parkinson's Disease Registry (CPDR): Study Design and Baseline Patient Characteristics.

BACKGROUND: There is a lack of large multicenter Parkinson's disease (PD) cohort studies and limited data on the natural history of PD in China. OBJECTIVES: The objective of this study was to launch the Chinese Parkinson's Disease Registry (CPDR) and to report its protocol, cross-sectional baseline data, and prospects for a comprehensive observational, longitudinal, multicenter study. METHODS: The CPDR recruited PD patients from 19 clinical sites across China between January 2018 and December 2020. Clinical data were collected prospectively using at least 17 core assessment scales. Patients were followed up for clinical outcomes through face-to-face interviews biennially. RESULTS: We launched the CPDR in China based on the Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network (PD-MDCNC). A total of 3148 PD patients were enrolled comprising 1623 men (51.6%) and 1525 women (48.4%). The proportions of early-onset PD (EOPD, age at onset ≤50 years) and late-onset PD (LOPD) were 897 (28.5%) and 2251 (71.5%), respectively. Stratification by age at onset showed that EOPD manifested milder motor and nonmotor phenotypes and was related to increased probability of dyskinesia. Comparison across genders suggested a slightly older average age at PD onset, milder motor symptoms, and a higher rate of developing levodopa-induced dyskinesias in women. CONCLUSIONS: The CPDR is one of the largest multicenter, observational, longitudinal, and natural history studies of PD in China. It offers an opportunity to expand the understanding of clinical features, genetic, imaging, and biological markers of PD progression. © 2022 International Parkinson and Movement Disorder Society.

Mutation analysis of MFSD8 in an amyotrophic lateral sclerosis cohort from mainland China.

Recent studies have suggested that rare variants in MFSD8 contribute to risk for frontotemporal dementia (FTD). Considering the common underlying pathogenesis and the shared genetic risk between amyotrophic lateral sclerosis (ALS) and FTD, we screened the coding region of MFSD8 in 551 unrelated patients with ALS (510 unrelated sporadic ALS and 41 familial ALS probands) from mainland China by whole-exome sequencing to assess its mutation frequency in patients with ALS and evaluate its association. Two rare deleterious variants, c.343G>A (p. V115M) and c.695T>C (p.L232P), were identified in this study. The variant c.695T>C (p.L232P) has not been previously reported and the carrier of this variant exhibits a relatively younger age of disease onset. Our studies provide some independent evidence showing that the rare variant p.L232P in MFSD8 might be a candidate risk factor for ALS. However, the relatively small sample size and the lack of patient-derived cells limit the power of the genetic exploration of this study, further robust multicenter studies with larger sizes and biological experiments with patient-derived cells are needed to elucidate the pathogenesis of the rare variant in MFSD8 in ALS.

The Expanding Phenotypic Spectrums Associated with ATP1A3 Mutation in a Family with Rapid-Onset Dystonia Parkinsonism.

INTRODUCTION: Rapid-onset dystonia parkinsonism (RDP), also referred to as Dystonia 12, is a rare autosomal dominant genetic disease characterized by abrupt onset of a rostrocaudal gradient of dystonia with prominent bulbar symptoms, and parkinsonian features, primarily bradykinesia and postural instability without tremor. The purpose of this study was to identify the genetic defect in a Chinese pedigree with familial RDP and to explore genotype-phenotype correlation. METHODS: A 3-generation Chinese Han pedigree consisting of 9 members and 3 patients with RDP, and 200 unrelated ethnically matched normal subjects were recruited in this study. Exome sequencing was performed in the proband, and Sanger sequencing was then conducted in other family members and 200 normal controls. RESULTS: In addition to the typical clinical manifestations of RDP, the proband and her sister presented tongue tremor which developed at the onset, and intriguingly the proband showed a "re-emergent" tongue tremor. Both the proband and her sister had a medical history of hyperthyroidism, and at the psychiatric interview they both received diagnoses of depression and anxiety. Excessive grammar errors existed in most sentences written by the proband, and this written-expression disorder occurred years before the onset of RDP. The mother of the proband presented tongue enlargement, oromandibular dystonia, and limb dystonia, which were not observed in her 2 daughters at the time of study. A missense variant, c.1838C>T (p.T613M), in the ATP1A3 gene, was identified in the 3 patients in the family and in 2 young children but was absent in family members without RDP and in the 200 normal controls. CONCLUSION: These findings may broaden the phenotypic spectrums of RDP with mutations in the ATP1A3 gene, provide new insights into the diagnosis of RDP, and have implications for genetic counseling.

Different iron deposition patterns in akinetic/rigid-dominant and tremor-dominant Parkinson's disease.

OBJECTIVE: The loss of dopaminergic cells and excessive iron deposition in some deep brain nuclei are associated with the pathophysiology of PD, and different clinical subtypes may indicate different pathological processes. This study was designed to investigate the relationships between regional iron in the cardinal subcortical nuclei and different clinical subtypes. PATIENTS AND METHODS: Nine Arkinetic/Rigid-dominant Parkinson's disease (PDAR) patients, eight Tremor-dominant (PDTD)patients and 10 matched healthy controls were recruited for this study. The iron content in 8 cardinal subcortical nuclei was measured through SWI sequence scanning (3.0 T), and different patterns of iron deposition were analyzed not only between the PD patients and HC groups but also between the different clinical subtypes. RESULTS: Compared with the healthy controls, the iron content in the substantia nigra pars compacta(SNc), substantia nigra pars reticulata(SNr) from both the severe and milder side in PD groups were significantly increased (P < 0.01 and P < 0.02 for SNc; both P < 0.01 for SNr), and the iron content in the GP of both the severe and milder side of the PDAR patients was significantly increased compared with the PDTD patients (P < 0.01 and P = 0.02, respectively) CONCLUSION: SWI is a very good technique for the in vivo assessment of subcortical nucleus iron content, and abnormal deposition of iron in the SNc and SNr is an obvious characteristic in PD patients. Furthermore, our data indicates that PDAR patients have higher iron content in the GP than PDTD patients and HCs, indicating that abnormal iron deposition in GP is related to the phenotype of Akinetic/Rigid in PD patients.

GCH1 variants contribute to the risk and earlier age-at-onset of Parkinson's disease: a two-cohort case-control study.

BACKGROUND: Common and rare variants of guanosine triphosphate cyclohydrolase 1 (GCH1) gene may play important roles in Parkinson's disease (PD). However, there is a lack of comprehensive analysis of GCH1 genotypes, especially in non-coding regions. The aim of this study was to explore the genetic characteristics of GCH1, including rare and common variants in coding and non-coding regions, in a large population of PD patients in Chinese mainland, as well as the phenotypic characteristics of GCH1 variant carriers. METHODS: In the first cohort of this case-control study, we performed whole-exome sequencing in 1555 patients with early-onset or familial PD and 2234 healthy controls; then in the second cohort, whole-genome sequencing was performed in sporadic late-onset PD samples (1962 patients), as well as 1279 controls. Variants at target GCH1 regions were extracted, and then genetic and detailed phenotypic data were analyzed using regression models and the sequence kernel association test. We also performed a meta-analysis to correlate deleterious GCH1 variants with age at onset (AAO) in PD patients. RESULTS: For coding variants, we identified a significant burden of GCH1 deleterious variants in early-onset or familial PD cases compared to controls (1.2% vs 0.1%, P < 0.0001). In the analysis of possible regulatory variants in GCH1 non-coding regions, rs12323905 (P = 0.001, odds ratio = 1.19, 95%CI 1.07-1.32) was significantly associated with PD, and variant sets in untranslated regions and intron regions, GCH1 brain-specific expression quantitative trait loci, and two possible promoter/enhancer (GH14J054857 and GH14J054880) were suggestively associated with PD. Genotype-phenotype correlation analysis revealed that the carriers of GCH1 deleterious variants manifested younger AAO (P < 0.0001), and had milder motor symptoms, milder fatigue symptoms and more autonomic nervous dysfunctions. Meta-analysis of six studies demonstrated 6.4-year earlier onset in GCH1 deleterious variant carriers (P = 0.0009). CONCLUSIONS: The results highlight the importance of deleterious variants and non-coding variants of GCH1 in PD in Chinese mainland and suggest that GCH1 mutation can influence the PD phenotype, which may help design experimental studies to elucidate the mechanisms of GCH1 in the pathogenesis of PD.

The role of genetics in Parkinson's disease: a large cohort study in Chinese mainland population.

This study aimed to determine the mutational spectrum of familial Parkinson's disease and sporadic early-onset Parkinson's disease (sEOPD) in a mainland Chinese population and the clinical features of mutation carriers. We performed multiplex ligation-dependent probe amplification assays and whole-exome sequencing for 1676 unrelated patients with Parkinson's disease in a mainland Chinese population, including 192 probands from families with autosomal-recessive Parkinson's disease, 242 probands from families with autosomal-dominant Parkinson's disease, and 1242 sEOPD patients (age at onset ≤ 50). According to standards and guidelines from the American College of Medical Genetics and Genomics, pathogenic/likely pathogenic variants in 23 known Parkinson's disease-associated genes occurred more frequently in the autosomal-recessive Parkinson's disease cohort (65 of 192, 33.85%) than in the autosomal-dominant Parkinson's disease cohort (10 of 242, 4.13%) and the sEOPD cohort (57 of 1242, 4.59%), which leads to an overall molecular diagnostic yield of 7.88% (132 of 1676). We found that PRKN was the most frequently mutated gene (n = 83, 4.95%) and present the first evidence of an SNCA duplication and LRRK2 p.N1437D variant in mainland China. In addition, several novel pathogenic/likely pathogenic variants including LRRK2 (p.V1447M and p.Y1645S), ATP13A2 (p.R735X and p.A819D), FBXO7 (p.G67E), LRP10 (c.322dupC/p.G109Rfs*51) and TMEM230 (c.429delT/p.P144Qfs*2) were identified in our cohort. Furthermore, the age at onset of the 132 probands with genetic diagnoses (median, 31.5 years) was about 14.5 years earlier than that of patients without molecular diagnoses (i.e. non-carriers, median 46.0 years). Specifically, the age at onset of Parkinson's disease patients with pathogenic/likely pathogenic variants in ATP13A2, PLA2G6, PRKN, or PINK1 was significantly lower than that of non-carriers, while the age at onset of carriers with other gene pathogenic/likely pathogenic variants was similar to that of non-carriers. The clinical spectrum of Parkinson's disease-associated gene carriers in this mainland Chinese population was similar to that of other populations. We also detected 61 probands with GBA possibly pathogenic variants (3.64%) and 59 probands with GBA p.L444P (3.52%). These results shed insight into the genetic spectrum and clinical manifestations of Parkinson's disease in mainland China and expand the existing repertoire of pathogenic or likely pathogenic variants involved in known Parkinson's disease-associated genes. Our data highlight the importance of genetic testing in Parkinson's disease patients with age at onset < 40 years, especially in those from families with a recessive inheritance pattern, who may benefit from early diagnosis and treatment.

Mutation analysis of CAPN1 in Chinese populations with spastic paraplegia and related neurodegenerative diseases.

BACKGROUND: Mutations in CAPN1 have recently been reported to cause the spastic paraplegia 76 (SPG76) subtype of hereditary spastic paraplegia (HSP). To investigate the role of CAPN1 in spastic paraplegia and other neurodegenerative diseases, including spinocerebellar ataxia (SCA), early-onset Parkinson's disease (EOPD), and amyotrophic lateral sclerosis (ALS) we conducted a mutation analysis of CAPN1 in a cohort of Chinese patients with SPG, SCA, EOPD, and ALS. METHODS: Variants of CAPN1 were detected in the three cohorts by Sanger or whole-exome sequencing, and all exons and exon-intron boundaries of CAPN1 were analysed. RESULTS: A novel CAPN1 splicing variant (NM_001198868: c.338-1G > A) identified in a familial SPG/SCA showed a complex phenotype, including spastic paraplegia, ataxia, and extensor plantar response. This mutation was confirmed by Sanger sequencing and completely co-segregated with the phenotypes. Sequencing of the cDNA from the three affected patients detected a guanine deletion (c.340_340delG) that was predicted to result in an early stop codon after 61 amino acids (p. D114Tfs*62). No CAPN1 pathogenic mutation was found in the EOPD or ALS groups. CONCLUSION: Our data reveal a novel CAPN1 mutation found in patients with SPG/SCA and emphasize the spastic and ataxic phenotypes of SPG76, but CAPN1 may not play a major role in EOPD and ALS.

Expansion of GGC repeat in the human-specific NOTCH2NLC gene is associated with essential tremor.

Essential tremor is one of the most common movement disorders. Despite its high prevalence and heritability, the genetic aetiology of essential tremor remains elusive. Up to now, only a few genes/loci have been identified, but these genes have not been replicated in other essential tremor families or cohorts. Here we report a genetic study in a cohort of 197 Chinese pedigrees clinically diagnosed with essential tremor. Using a comprehensive strategy combining linkage analysis, whole-exome sequencing, long-read whole-genome sequencing, repeat-primed polymerase chain reaction and GC-rich polymerase chain reaction, we identified an abnormal GGC repeat expansion in the 5' region of the NOTCH2NLC gene that co-segregated with disease in 11 essential tremor families (5.58%) from our cohort. Clinically, probands that had an abnormal GGC repeat expansion were found to have more severe tremor phenotypes, lower activities of daily living ability. Obvious genetic anticipation was also detected in these 11 essential tremor-positive families. These results indicate that abnormal GGC repeat expansion in the 5' region of NOTCH2NLC gene is associated with essential tremor, and provide strong evidence that essential tremor is a family of diseases with high clinical and genetic heterogeneities.

[Effects of moxibustion on the structure and function of blood brain barrier in Alzheimer's disease model rats].

OBJECTIVE: To investigate the effects of moxibustion on the structure and function of blood-brain barrier in Alzheimer's disease (AD) model rats. METHODS: Forty-eight SD rats were randomly divided into 4 groups: normal control group, sham operation group, model group, moxibustion group. Model group and moxibustion group rats were injected with aggregated Aß25-35 by bilateral hippocampus. In the rat model, the sham-operated group was injected with the same amount of normal saline in the bilateral hippocampus, and the normal group was not treated. After successful modeling, the moxibustion treatment was given at 2～3 cm above the Baihui, Shenshu and Yintang points of the moxibustion group rats, each time for 10 min, once a day, continuous treatment for 21 d. The Morris water maze test was used to evaluate the learning and memory ability of rats in each group. The Evans blue method was used to detect the permeability of blood-brain barrier. The ultrastructure of blood-brain barrier was observed under electron microscope. The matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) positive cells in hippocampus were detected by immunohistochemistry. RESULTS: Compared with the sham operation group, the escape latency was significantly increased (P＜0.01), and the space exploration time was decreased (P＜0.01), the learning and memory function in model group was impaired seriously, the Evans blue content in the brain was increased significantly (P＜0.01), the perivascular edema became larger, and the blood-brain barrier structure function was impaired. At the same time, the positive expressions of MMP-2 and MMP-9 in hippocampus were increased significantly (P＜0.01). Compared with model group, the learning and memory ability in moxibustion group rats was enhanced (P＜ 0.05), the content of Evans blue in the brain was decreased (P＜0.05), the degree of perivascular edema was reduced, and the damage of blood-brain barrier was improved. Positive expressions of MMP-2 and MMP-9 in hippocampus were decreased (P＜0.05 or P＜ 0.01). CONCLUSION: Moxibustion can decrease the expressions of MMP-2 and MMP-9, and reduce the damage of the structure and function of blood-brain barrier, thereby improving the learning and memory ability of AD model rats, and exerting therapeutic effects.

TMEM230 mutation analysis in Parkinson's disease in a Chinese population.

Mutations in TMEM230 were identified as a genetic factor for Parkinson's disease (PD) with typical clinical symptoms and Lewy bodies in a North American population, and a highly prevalent TMEM230 mutation, c.550_552delTAGinsCCCGGG (p.*184ProGlyext*5), was found in 7 Chinese families. In the present study, we investigated the prevalence of TMEM230 mutations in a large cohort of Chinese PD patients and healthy controls individuals from mainland China. We sequenced all exons and exon-intron boundaries of TMEM230 in Chinese Han population including 1235 patients with PD and 1252 healthy control individuals. As a result, we did not detect any pathogenic mutation of TMEM230 in 192 probands with familial PD or 1043 sporadic PD patients. However, we did detect a synonymous variant c.357G>A p.Gly119Gly in a case of familial PD and the 3' UTR+3G>T variant in 2 sporadic PD patients. These results suggested that TMEM230 mutation may not be a common genetic factor for Chinese familial and sporadic PD patients.