A systematic review of salivary biomarkers in Parkinson's disease

The search fo r reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis,to detect neurodegeneration from the prodromal phase and to enforce disease-modifying therapies.Despite the need for non-invasively accessible biomarke rs,the majo rity of the studies have pointed to cerebrospinal fluid or peripheral biopsies biomarkers,which require invasive collection procedures.Saliva represents an easily accessible biofluid and an incredibly wide source of molecular biomarkers.In the present study,after presenting the morphological and biological bases for looking at saliva in the search of biomarkers for Parkinson's disease,we systematically reviewed the results achieved so far in the saliva of different cohorts of Parkinson's disease patients.A comprehensive literature search on PubMed and SCOPUS led to the discovery of 289articles.After screening and exclusion,34 relevant articles were derived fo r systematic review.Alpha-synuclein,the histopathological hallmark of Parkinson's disease,has been the most investigated Parkinson's disease biomarker in saliva,with oligomeric alphasynuclein consistently found increased in Parkinson's disease patients in comparison to healthy controls,while conflicting results have been reported regarding the levels of total alpha-synuclein and phosphorylated alpha-synuclein,and few studies described an increased oligomeric alpha-synuclein/total alpha-synuclein ratio in Parkinson's disease.Beyond alpha-synuclein,other biomarkers to rgeting diffe rent molecular pathways have been explored in the saliva of Parkinson's disease patients:total tau,phosphorylated tau,amyloid-β1-42(pathological protein aggregation biomarkers);DJ-1,heme-oxygenase-l,metabolites(alte red energy homeostasis biomarkers);MAPLC-3beta(aberrant proteostasis biomarker);cortisol,tumor necrosis factor-alpha(inflammation biomarkers);DNA methylation,miRNA(DNA/RNA defects biomarkers);acetylcholinesterase activity(synaptic and neuronal network dysfunction biomarkers);Raman spectra,proteome,and caffeine.Despite a few studies investigating biomarkers to rgeting molecular pathways different from alpha-synuclein in Parkinson's disease,these results should be replicated and observed in studies on larger cohorts,considering the potential role of these biomarkers in determining the molecular variance among Parkinson's disease subtypes.Although the need fo r standardization in sample collection and processing,salivary-based biomarkers studies have reported encouraging results,calling for large-scale longitudinal studies and multicentric assessments,given the great molecular potentials and the non-invasive accessibility of saliva.

Changes in Salivary and Plasma Markers during and Following Short-Term Maximal Aerobic Exercise Assessed during Cognitive Assessment

This study assessed multiple salivary and plasma markers before and after incremental short-term maximal aerobic exercise and in a non-exercising control in conjunction with cognitive testing. Subjects: Apparently healthy 18 - 30 years old low CVD risk females participated (n = 19). Methods: Subjects completed two conditions: 1) exercise: short maximal treadmill exercise and cognitive assessment pre- and post-exercise and, 2) non-exercise: with cognitive assessment timed to match testing in the exercising condition. Non-stimulated, timed salivary samples and venous blood were collected before and after exercise and after recovery. Results: Saliva: Over time α-amylase increased in both exercise and non-exercising conditions. Exercise had increases in α-amylase at time matched control points up to 36% greater than the non-exercising conditions. Following exercise and recovery from exercise α-amylase in-creased compared to baseline (ranging from 47% to 290%). Baseline cortisol was 33% higher than post-exercise and 59% higher than recovery irrespective of exercise. Plasma: NEFA was 50% higher at post-exercise and recovery compared to baseline without exercise and 36% higher at post-exercise and recovery compared to baseline with exercise. Glucose and lactate were, 18% and 50% higher respectively, after exercise compared to baseline and recovery with exercise. Post-exercise glycerol was 11% higher than recovery. Differences between Conditions: Post-exercise glucose and lactate were 20% and 40% higher respectively with exercise. Glycerol was 11% lower after exercise. Conclusions: We demonstrated that acute exercise coupled with cognitive task increased α-amylase levels, but not cortisol, potentially due to a differential stress response, but most likely due to the timing of sample collection.

A Comparison of the Effect of 20-and 40-Min Session Durations of External Counterpulsation on Neuromuscular Function,Cortisol and Comfort in Physically Active Young Men

Objectives External Counterpulsation (ECP) is a well-established treatment for coronary disease,with interest growing in the potential to act as a sports recovery modality or pre-performance strategy.This pilot study compared the effects of dif-ferent ECP durations upon neuromuscular function (NF),cortisol and subjective perceptions in a rested state.Methods Eleven physically active male volunteers received two ECP treatments (Renew Sport,Singapore) of differing duration (20-min and 40-min) in a randomised,repeated measures crossover design.Testing occurred pre-ECP,post-ECP,and 24-h post-ECP.NF testing comprised counter-movement jumps (CMJs) and 6-s sprint cycling.Saliva samples were analysed for cortisol.Rate of Perceived Exertion (RPE,6 to 20) and Bipolar Comfort Scales (-10 to 10) quantified partici-pants' experiences,and ECP duration preference was examined.Repeated measures ANOVA and effect size (ES:Cohen's d) analysed NF and cortisol results.Paired t-tests analysed RPE and comfort ratings.Results ECP demonstrated no effect,neither positive nor negative,upon NF outcome measures in both groups.A trend of reduced salivary cortisol levels across both groups following ECP was observed (P =0.066).No RPE difference existed between groups.20-min of ECP was rated as significantly more comfortable than 40-min (P < 0.05) and participants pre-dominantly identified the 20-min ECP session as "more acceptable".Conclusions These results indicate that there were no effects for either duration upon the defined outcome measures,and thus,in these circumstances,no differences between the two durations were observed with respect to effects upon NF and salivary cortisol.The use of ECP warrants further investigation for potential benefits to performance before it can be proposed as an effective preparatory modality.