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Abstract Background Minimally invasive specific biomarkers of neurodegenerative diseases (NDs) would facilitate patient selection and disease progression monitoring. We describe the assessment of circulating brain-enriched microRNAs as potential biomarkers for Alzheimer’s disease (AD), frontotemporal dementia (FTD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). Methods In this case-control study, the plasma samples were collected from 250 research participants with a clinical diagnosis of AD, FTD, PD, and ALS, as well as from age- and sex-matched control subjects (n = 50 for each group), recruited from 2003 to 2015 at the University of Pennsylvania Health System, including the Alzheimer’s Disease Center, the Parkinson’s Disease and Movement Disorders Center, the Frontotemporal Degeneration Center, and the Amyotrophic Lateral Sclerosis Clinic. Each group was randomly divided into training and confirmation sets of equal size. To evaluate the potential of circulating microRNAs enriched in specific brain regions affected by NDs and present in synapses as biomarkers of NDs, the levels of 37 brain-enriched and inflammation-associated microRNAs in the plasma of all participants were measured using individual qRT-PCR. A “microRNA pair” approach was used for data normalization. Results MicroRNA pairs and their combinations (classifiers) capable of differentiating NDs from control and from each other were defined using independently and jointly analyzed training and confirmation datasets. AD, PD, FTD, and ALS are differentiated from control with accuracy of 0.89, 0.90, 0.88, and 0.83 (AUCs, 0.96, 0.96, 0.94, and 0.93), respectively; NDs are differentiated from each other with accuracy ranging from 0.77 (AUC, 0.87) for AD vs. FTD to 0.93 (AUC, 0.98) for AD vs. ALS. The data further indicate sex dependence of some microRNA markers. The average increase in accuracy in distinguishing ND from control for all and male/female groups is 0.06; the largest increase is for ALS, from 0.83 for all participants to 0.92/0.98 for male/female participants. Conclusions The work presented here suggests the possibility of developing microRNA-based diagnostics for detection and differentiation of NDs. Larger multicenter clinical studies are needed to further evaluate circulating brain-enriched microRNAs as biomarkers for NDs and to investigate their association with other ND biomarkers in clinical trial settings.

SUMMARY: Elman LB, Siderowf AD, McCluskey LF: Nocturnal oximetry: Utility in the respiratory management of amyotrophic lateral sclerosis. Am J Phys Med Rehabil 2003;82:866-870.OBJECTIVE Current recommendations are to institute nocturnal nasal ventilation for amyotrophic lateral sclerosis patients with a forced vital capacity (FVC) of <50% of predicted normal. The purpose of this study was to determine whether this is appropriate.DESIGN A total of 87 nocturnal oximetry evaluations were performed on 78 consecutive amyotrophic lateral sclerosis patients symptomatic for sleep-disordered breathing. Nocturnal oximetry measurements were compared for those with FVC >50% vs. those with FVC of <50% of normal. FVC was measured sitting and supine.RESULTS A considerable number of these symptomatic patients manifested evidence of nocturnal hypoxemia as measured by oximetry. However, there was no significant difference between patients with sitting percentage-predicted FVC above and below 50% predicted in minimum oxygen saturation, mean oxygen saturation, percentage of time spent with oxygen saturation of <88%, and number of events per hour. There was no significant difference between patients with supine percentage-predicted FVC above and below 50% predicted in minimum oxygen saturation, mean oxygen saturation, percentage of time spent with oxygen saturation of <88%, and number of events per hour.CONCLUSION The recommendation that FVC be <50% of normal is inappropriate for justifying introduction of nocturnal nasal ventilation. Many patients are symptomatic at higher FVC and manifest evidence of nocturnal hypoxemia. Nocturnal oximetry adds additional practical information for justifying earlier respiratory intervention for symptomatic patients. [ABSTRACT FROM AUTHOR]