Salivary biomarkers in Alzheimer's disease.

OBJECTIVES: The objective of this study was to evaluate the changes that can occur in saliva components in patients with Alzheimer's disease (AD) of different severity and determine if any of these components could be a biomarker of this disease. Therefore, a panel of selected analytes related to the amyloid cascade, the immune and adrenergic systems, among others, were analyzed in the saliva of patients with Alzheimer's disease. METHODS: A total of 152 patients with AD and controls were included. The severity of the disease was established according to the Global Deterioration Scale. Unstimulated whole saliva was collected. RESULTS: Salivary amyloid-ß42 was significantly lower, and complement C4 was significantly higher in the patients with AD than in the controls (p < 0.05 in both cases). Only complement C4 maintained its significant effect in the multivariate regression analysis. However, the area under the receiver operating characteristic curve of C4 was 0.613. No changes were found in any analyte regarding the severity of the disease. CONCLUSIONS: A decrease in amyloid-ß42 and an increase in complement C4 were detected in the saliva of patients with AD, but the changes did not show a high diagnostic performance for the detection of AD and were not associated with its severity. CLINICAL RELEVANCE: Although some analytes showed significant differences in saliva in patients with AD, in our study conditions the salivary biomarkers analyzed were not of enough diagnostic utility for being used in routine.

Pharmacogenetic Profiling in High-Risk Soft Tissue Sarcomas Treated with Neoadjuvant Chemotherapy.

Neoadjuvant chemotherapy based on anthracyclines and ifosfamide for high-risk soft tissue sarcomas (STS) of the extremities and trunk is a controversial treatment option. There are substantial interindividual differences in clinical outcomes in patients treated with neoadjuvant chemotherapy. The aim of this study was to evaluate, as biomarkers, polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters, or drug targets and their association with toxicity and survival in STS patients treated with neoadjuvant chemotherapy. We analysed variants in genes involved in anthracycline metabolism (ABCB1, ABCC2, NQO1, CBR3, and SLC22A16) and in ifosfamide catabolism (ALDH1A1) in 79 treated patients. Two genes showed significant association after adjusted multivariate analysis: ABCC2 and ALDH1A1. In patients treated with anthracyclines, ABCC2 rs3740066 was associated with risk of febrile neutropenia (p = 0.031), and with decreased overall survival (OS) (p = 0.024). ABCC2 rs2273697 was associated with recurrence-free survival (RFS) (p = 0.024). In patients treated with ifosfamide, ALDH1A1 rs3764435 was associated with RFS (p = 0.046). Our pharmacogenetic study shows for the first time that variants in genes regulating the metabolism of neoadjuvant chemotherapy may be helpful to predict toxicity and survival benefit in high-risk STS treated with neoadjuvant chemotherapy. Further validation studies are needed to establish their clinical utility.