MicroRNA-29c-3p in dual-labeled exosome is a potential diagnostic marker of subjective cognitive decline.

OBJECTIVE: The present study aimed to determine whether peripheral blood neural cell adhesion molecule (NCAM)/amphiphysin 1 dual-labeled exosomal proteins and microRNAs (miRs) might serve as a marker for the early diagnosis of Alzheimer's disease (AD). METHODS: This observational, retrospective, multicenter study used a two-stage design conducted in Beijing and Shanghai, China. The subjects included 76 patients with subjective cognitive decline (SCD), 80 with amnestic mild cognitive impairment (aMCI), 76 with dementia of Alzheimer's type (AD), 40 with vascular dementia (VaD), and 40 controls in the discovery stage. These results were confirmed in the verification stage. The levels of Aß42, Aß42/40, T-Tau, P-T181-tau, neurofilament light chain (NfL), and miR-29c-3p in peripheral blood amphiphysin 1 single-labeled and NCAM/amphiphysin 1 dual-labeled exosomes were captured and detected by immunoassay. RESULTS: In the discovery stage, the levels of Aß42 and miR-29c-3p in peripheral blood NCAM/amphiphysin 1 dual-labeled exosome of the SCD group were significantly higher than those in control and VaD groups (all P < 0.05). The verification stage further confirmed the results of the discovery stage. Plasma NCAM/amphiphysin 1 dual-labeled exosomal miR-29c-3p showed a good diagnostic performance. The NCAM/amphiphysin 1 dual-labeled exosomal miR-29c-3p had the highest AUC for diagnosis of SCD. The levels of Aß42, Aß42/40, Tau, P-T181-tau, and miR-29c-3p in peripheral blood exosomes were correlated to those in CSF (all P < 0.05). The combination of exosomal biomarkers had slightly higher diagnostic efficiency than the individual biomarkers and that the exosomal biomarkers had the same diagnostic power as the CSF biomarkers. CONCLUSION: The plasma NCAM/amphiphysin 1 dual-labeled exosomal miR-29c-3p had potential advantages in the diagnosis of SCD.

Amyloid-ß protein and MicroRNA-384 in NCAM-Labeled exosomes from peripheral blood are potential diagnostic markers for Alzheimer's disease.

OBJECTIVE: We aimed to establish a method to determine whether amyloid-ß (Aß) protein and miR-384 in peripheral blood neural cell adhesion molecule (NCAM)/ATP-binding cassette transporter A1 (ABCA1) dual-labeled exosomes may serve as diagnostic markers for the diagnosis of Alzheimer's disease (AD). METHODS: This was a multicenter study using a two-stage design. The subjects included 45 subjective cognitive decline (SCD) patients, 50 amnesic mild cognitive impairment (aMCI) patients, 40 AD patients, and 30 controls in the discovery stage. The results were validated in the verification stage in 47 SCD patients, 45 aMCI patients, 45 AD patients, and 30 controls. NCAM single-labeled and NCAM/ABCA1 double-labeled exosomes in the peripheral blood were captured and detected by immunoassay. RESULTS: The Aß42, Aß42/40 , Tau, P-T181-tau, and miR-384 levels in NCAM single-labeled and NCAM/ABCA1 double-labeled exosomes of the aMCI and AD groups were significantly higher than those of the SCD, control, and vascular dementia (VaD) groups (all p < 0.05). The Aß42 and miR-384 levels in NCAM/ABCA1 dual-labeled exosomes of the aMCI and AD groups were higher than those of the control and VaD groups (all p < 0.05). The exosomal Aß42, Aß42/40 , Tau, P-T181-tau, and miR-384 levels in peripheral blood were correlated with those in cerebrospinal fluid (all p < 0.05). CONCLUSION: This study, for the first time, established a method that sorts specific surface marker exosomes using a two-step immune capture technology. The plasma NCAM/ABCA1 dual-labeled exosomal Aß42/40 and miR-384 had potential advantages in the diagnosis of SCD.

The association between urinary Alzheimer-associated neuronal thread protein and cognitive impairment in late-life depression: a controlled pilot study.

Accumulation of tau protein is associated with both Alzheimer's disease (AD) and late-life depression (LLD). Alzheimer-associated neuronal thread protein (AD7c-NTP), which is closely linked with the tau protein, is elevated in the cerebrospinal fluid and urine of AD patients. This study examined the association between urinary AD7c-NTP and late-life depression with cognitive impairment. One hundred and thirty-eight subjects were recruited into late-life depression with cognitive impairment (LLD-CI, n=52), late-life depression without cognitive impairment (LLD-NCI, n=29), AD (n=27), and healthy control (HC, n=30) groups. The level of urinary AD7c-NTP was measured using the enzyme-linked immunosorbent assay method. The Montreal Cognitive Assessment scale (MoCA), Hamilton Rating Scale for Depression (HRSD) and Hamilton Anxiety Rating Scale (HAMA) were used to assess cognitive functions and depressive and anxiety symptoms in the AD and LLD groups. Urinary levels of AD7c-NTP in the LLD-CI group (1.0±0.7ng/ml) were significantly higher than both the LLD-NCI (0.5±0.3ng/ml) and HC groups (0.5±0.3ng/ml), but lower than in the AD group (1.6±1.7 ng/ml). No significant associations were found in the level of urinary AD7c-NTP in relation to age, gender, education and MoCA in the LLD-CI group. The level of urinary AD7c-NTP appears to be associated with cognitive impairment in late-life depression and may be a potential biomarker for early identification of cognitive impairment in LLD.

Association between COMT gene polymorphisms, clinical symptoms, and cognitive functions in Han Chinese patients with schizophrenia.

AIM: Catechol-O-methyltransferase (COMT) gene variants may be involved in the pathogenesis of psychotic symptoms, and associated especially with negative symptom in schizophrenia, but their roles in cognitive function and treatment response remain unclear. The aim of this study was to explore the association between COMT gene polymorphisms, clinical symptoms (including cognitive function), and treatment response to antipsychotic medications in patients with schizophrenia. PATIENTS AND METHODS: A total of 200 Han Chinese inpatients with schizophrenia were recruited in accordance with Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV). In total, 96 of them completed assessments at baseline and after 8 weeks of antipsychotic treatment. Clinical symptoms were assessed using the Positive And Negative Syndrome Scale (PANSS), and cognitive function was evaluated using the Verbal Fluency Test, Trail Making Test A-B, Stroop Color-Word Test, and Wisconsin Card Sorting Test. Two single nucleotide polymorphisms, rs4680 and rs165599, on the COMT gene were genotyped. RESULTS: At baseline, we found no significant genotypic association between rs4680 and clinical symptoms or cognitive function. After 8 weeks of antipsychotic treatment, compared with patients with GG genotype, patients with AA/AG genotypes at rs4680 showed significantly higher scores on PANSS total, both at baseline and at the end of 8 weeks, especially in negative and general psychopathology symptoms. Patients with GG at rs165599 scored significantly higher on the Stroop test, suggesting better cognitive performance after 8 weeks of treatment. No significant association was found between rs165599 genotype and psychiatric symptoms as assessed by the PANSS and cognitive function tests at baseline. CONCLUSION: Our findings suggest that the COMT gene polymorphisms may influence the response to antipsychotic treatment in Han Chinese patients with schizophrenia.

Serum brain-derived neurotrophic factor levels associate with cognitive improvement in patients with schizophrenia treated with electroacupuncture.

Accumulating evidence supports that acupuncture has been successfully used for the treatment of neurological disorders to improve cognitive function. This study was set to evaluate the efficacy of electroacupuncture (EA, using two acupoints: Baihui and Shenting) on clinical symptoms, cognitive function and brain-derived neurotrophic factor (BDNF) levels in patients with schizophrenia. Sixty-one inpatients diagnosed schizophrenia with DSM-IV criteria were recruited. The participants were randomly divided into an experimental group (n=30) and a control group (n=31). The patients were evaluated using the Positive and Negative Symptom Scale (PANSS), the Wisconsin Card Sorting Test (WCST) and Wechsler Memory Scale (WMS) at baseline and after EA treatment. There were no significant differences in the PANSS scores and serum BDNF levels between the experimental group and the control group, either at baseline or at the end of the 4-week study period. However, the EA treatment appeared to have significant benefits on memory and moderate benefits on executive functions and problem solving. Significant positive correlation was observed between the increase of BDNF levels and memory improvement after EA treatment. Our results indicated that EA treatment could improve cognitive function, and the cognitive benefits positively associate with serum BDNF levels in patients with schizophrenia.

Overexpression of serotonin receptor and transporter mRNA in blood leukocytes of antipsychotic-free and antipsychotic-naïve schizophrenic patients: gender differences.

BACKGROUND: Abnormal serotonin (5-HT) activity has been implicated in schizophrenia. However, the role of 5-HT receptors and transporter (5-HTT) in male and female schizophrenia remains largely unknown. Recent studies suggest that 5-HT system expressed in the peripheral leukocyte could be a marker of the illness. METHODS: 46 acute schizophrenic patients (male=35, female=11) that were antipsychotic-naïve or antipsychotic-free for at least three months (average=27.3 months) and 44 age- and sex-matched healthy subjects (male=24, female=20) were included for blood leukocytes expression of 5-HT(1A), 5-HT(2A) and 5-HT(7) receptor and 5-HTT mRNA, using real-time PCR technique. RESULTS: ANOVA analysis showed a significant increase of 5HT(2A) mRNA and 5-HTT mRNA (each >2-fold, P<0.01) and a trend increase of 5HT(1A) mRNA (P<0.15) and 5-HT(7) mRNA (P<0.09) level in blood leukocytes of pooled schizophrenic patients than in the healthy subjects. The elevation was mainly found in the male patients. Within-sex analysis showed that the male antipsychotic-free schizophrenic patients exhibited greater 5-HT(1A) and 5-HT(7) mRNA expression (P<0.05, each ) whereas female antipsychotic-free patients showed decreased 5-HT(1A) mRNA expression (P<0.05) when compared with the male and female healthy subjects, respectively. The correlations between 5-HT mRNA and clinical symptoms (PANSS scales) were calculated. CONCLUSIONS: The present findings showed an abnormal expression of leukocyte 5-HT system in antipsychotic-free and antipsychotic-naïve schizophrenia especially in the male patients. Because of the greater accumulative dose of antipsychotics in the relatively smaller number of the female patients of the study, further study is needed to confirm the present findings. If replicated, blood serotonergic markers could add to the diagnosis and individualized pharmacotherapy of schizophrenic patients, especially the male patients.

[An association study between GRIN1, BDNF genes and bipolar disorder].

To evaluate the role of inherited gene variations in GRIN1 (glutamate receptor, ionotropic NMDA1), BDNF (brain derived neurotrophic factor) genes in human bipolar disorder, we selected 4 single nucleotide polymorphisms in GRIN1, BDNF (2 SNPs in each gene) and made SNPs analysis in 100 unrelated cases and 100 controls by TaqMan. Then we compared genotypes differences between cases and controls. The software SHEsis was also used to make haplotype analysis. The significant results were obtained, showing that the SNPs in GRIN1 gene were related to the BP (P < 0.05). In addition, the combined haplotype T/G had a significant difference in the two groups (P < 0.05). The SNPs in BDNF gene showed no statistical significance. These results confirm that the GRIN1 gene confers susceptibility to bipolar disorder.

Plasma S-100B protein in Chinese patients with schizophrenia: comparison with healthy controls and effect of antipsychotics treatment.

PURPOSE: To examine the possibility that structural damage to the brain may play a role in the pathogenesis of schizophrenia by measuring the level of plasma S-100B, a calcium-binding protein found predominantly in the cytosol of glial cells. METHOD: Fifty-seven Chinese psychiatric inpatients who met DSM-IV diagnosis of schizophrenia and 60 healthy controls were enrolled in the study. Patients were assessed with the Positive and Negative Symptoms Scale (PANSS) at admission and at 12 weeks after treatment. Plasma samples were collected from patients and controls and S-100B protein was assayed using ELISA. RESULTS: (1) 29 of 57 patients (50.9%) showed increased S-100B level compared to the mean level of 60 healthy controls (p<0.005) vs. only 1 of 60 (1.67%) controls. The S-100B levels of unmedicated (0.119+/-0.059microg/L) and medicated patients (0.117+/-.0.057microg/L) were significantly higher than controls (0.067+/-0.022microg/L, both p<0.001), and S-100B levels of unmedicated patients were higher than those of medicated patients (p=0.024); (2) at admission, S-100B level was positively correlated with total score of PANSS (r=0.269, p=0.043), especially with negative subscore of PANSS (r=0.306, p=0.021), but the correlation was no longer present after patients were treated by anti-psychotic agents. CONCLUSION: The S-100B levels of patients with schizophrenia are significantly higher than that of healthy controls, and the S-100B level is associated with severity of psychopathology, particularly negative symptoms, indicating that patients with schizophrenia may suffer structural damage to central nervous system. The concentration of S-100B may also be associated with treatment progress.