A targeted proteomic multiplex CSF assay identifies increased malate dehydrogenase and other neurodegenerative biomarkers in individuals with Alzheimer's disease pathology.

Alzheimer's disease (AD) is the most common cause of dementia. Biomarkers are required to identify individuals in the preclinical phase, explain phenotypic diversity, measure progression and estimate prognosis. The development of assays to validate candidate biomarkers is costly and time-consuming. Targeted proteomics is an attractive means of quantifying novel proteins in cerebrospinal and other fluids, and has potential to help overcome this bottleneck in biomarker development. We used a previously validated multiplexed 10-min, targeted proteomic assay to assess 54 candidate cerebrospinal fluid (CSF) biomarkers in two independent cohorts comprising individuals with neurodegenerative dementias and healthy controls. Individuals were classified as 'AD' or 'non-AD' on the basis of their CSF T-tau and amyloid Aß1-42 profile measured using enzyme-linked immunosorbent assay; biomarkers of interest were compared using univariate and multivariate analyses. In all, 35/31 individuals in Cohort 1 and 46/36 in Cohort 2 fulfilled criteria for AD/non-AD profile CSF, respectively. After adjustment for multiple comparisons, five proteins were elevated significantly in AD CSF compared with non-AD CSF in both cohorts: malate dehydrogenase; total APOE; chitinase-3-like protein 1 (YKL-40); osteopontin and cystatin C. In an independent multivariate orthogonal projection to latent structures discriminant analysis (OPLS-DA), these proteins were also identified as major contributors to the separation between AD and non-AD in both cohorts. Independent of CSF Aß1-42 and tau, a combination of these biomarkers differentiated AD and non-AD with an area under curve (AUC)=0.88. This targeted proteomic multiple reaction monitoring (MRM)-based assay can simultaneously and rapidly measure multiple candidate CSF biomarkers. Applying this technique to AD we demonstrate differences in proteins involved in glucose metabolism and neuroinflammation that collectively have potential clinical diagnostic utility.

Body mass index, sexual difficulties and sexual satisfaction among people in regular heterosexual relationships: a population-based study.

BACKGROUND/AIMS: The aims of this study were to clarify the relationship between body mass index (BMI) and sexual difficulties and to investigate if BMI influenced sexual satisfaction, over and above the effects of sexual difficulties. METHODS: Cross-sectional analyses of a nationally representative computer-assisted telephone interview. Eight thousand, six hundred and fifty-six respondents were recruited by random digit dialling in 2004-2005. Only those in a sexually active, heterosexual relationship were included in the current analyses. RESULTS: After adjustments for demographic factors, both overweight and obese male and female participants were more likely to report worrying during sex about whether their body was unattractive. Among women, associations were also found between higher BMI and lack of interest in sex. No other significant associations between BMI and sexual difficulties were evident. There was an association between BMI and extreme physical pleasure for women but not men over and above the effects of sexual difficulties, with obese women being more likely than normal weight women to report extreme physical pleasure. No associations were found for either men or women between BMI and whether or not they reported extreme emotional or sexual satisfaction with their relationship. CONCLUSIONS: With the exception of body image difficulties, there is little association between BMI and self-reported sexual difficulties. Furthermore, extreme sexual and emotional satisfaction appeared to be associated with the presence or absence of sexual difficulties and not overly influenced by BMI. Overall, clinicians and patients should be aware that being overweight is not necessarily detrimental to sexual functioning.

Application of label-free absolute quantitative proteomics in human gingival crevicular fluid by LC/MS E (gingival exudatome).

Periodontal disease is perhaps the most common infectious disease in humans. Gingival crevicular fluid (GCF) is a local inflammatory exudate of the periodontal tissues. Its composition greatly varies between health and periodontal disease. GCF collection is rapid and noninvasive, but previous approaches aiming to analyze its composition have mainly involved single protein biomarkers. The aim of this study was to perform analysis of the GCF exudatome from healthy and periodontally diseased sites by LC/MS(E), a label-free mass spectrometry method that enables simultaneous protein identification and absolute quantification in biological fluids. In total, 154 proteins of human, bacterial, and viral origin were identified in the 40 GCF samples obtained from the 10 subjects (five healthy and five generalized aggressive periodontitis). The proportion of bacterial, viral, and yeast protein was increased in disease, compared to health. The presence of host defense-related proteins, such as Cystatin-B and defensins, was confirmed to be present only in health. Among the newly identified GCF proteins were L-plastin detected only in disease (15.6 +/- 12.1 fmol) and Annexin-1 detected in 5-fold higher levels in health. Nevertheless, pro-inflammatory cytokines or periodontal pathogen proteins were rarely detected. Conclusively, the LC/MS(E) technology may facilitate characterization of GCF proteome in periodontal health and disease, thus conferring prognostic and diagnostic value. Larger cohort studies are required to characterize the complete GCF proteome in health and disease.