P1‐021: Diurnal and intersubject variability of cerebrospinal fluid biomarkers, Aβ‐40/42, alpha‐synuclein and DJ‐1 in healthy volunteers

Ereshefsky, Larry; Frasier, Mark; Yen, Mark; Jhee, Stanford; Marek, Kenneth; Taylor, Peggy; Sherman, Molly Hamilton; Caspell, Chelsea; Coffey, Chris; Schlossmacher, Michael G.; Sherer, Todd

doi:10.1016/j.jalz.2012.05.296

Cited by 1 publication

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“…Vital signs were taken regularly, and subjects remained in the clinic for at least 24 h following sample collections for monitoring, and a final neurological examination before discharge. Study procedures were safe and well tolerated with no serious adverse events related to the procedure [ 43 ].…”

Section: Methodsmentioning

confidence: 99%

“…The first part of this study evaluated the stability of key CSF biomarkers, alpha-synuclein, DJ-1, and Abeta1-42 in young healthy volunteers in a two period study using the same sampling schedule as outlined here. A minimum of two weeks separated the repeat sampling for blood and CSF [ 43 ]. Given that endogenous cortisol levels peak in the morning [ 39 ] and can affect cytokine levels [ 40 , 41 ], we hypothesized that a subset of inflammatory factors in central and/or peripheral compartments display normal diurnal variations in HC subjects and these may be disrupted in patients with PD.…”

Section: Introductionmentioning

confidence: 99%

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Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson’s disease

Eidson

Kannarkat

Barnum

et al. 2017

J Neuroinflammation

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BackgroundEfforts to identify fluid biomarkers of Parkinson’s disease (PD) have intensified in the last decade. As the role of inflammation in PD pathophysiology becomes increasingly recognized, investigators aim to define inflammatory signatures to help elucidate underlying mechanisms of disease pathogenesis and aid in identification of patients with inflammatory endophenotypes that could benefit from immunomodulatory interventions. However, discordant results in the literature and a lack of information regarding the stability of inflammatory factors over a 24-h period have hampered progress.MethodsHere, we measured inflammatory proteins in serum and CSF of a small cohort of PD (n = 12) and age-matched healthy control (HC) subjects (n = 6) at 11 time points across 24 h to (1) identify potential diurnal variation, (2) reveal differences in PD vs HC, and (3) to correlate with CSF levels of amyloid β (Aβ) and α-synuclein in an effort to generate data-driven hypotheses regarding candidate biomarkers of PD.ResultsDespite significant variability in other factors, a repeated measures two-way analysis of variance by time and disease state for each analyte revealed that serum IFNγ, TNF, and neutrophil gelatinase-associated lipocalin (NGAL) were stable across 24 h and different between HC and PD. Regression analysis revealed that C-reactive protein (CRP) was the only factor with a strong linear relationship between CSF and serum. PD and HC subjects showed significantly different relationships between CSF Aβ proteins and α-synuclein and specific inflammatory factors, and CSF IFNγ and serum IL-8 positively correlated with clinical measures of PD. Finally, linear discriminant analysis revealed that serum TNF and CSF α-synuclein discriminated between PD and HC with a minimum of 82% sensitivity and 83% specificity.ConclusionsOur findings identify a panel of inflammatory factors in serum and CSF that can be reliably measured, distinguish between PD and HC, and monitor inflammation as disease progresses or in response to interventional therapies. This panel may aid in generating hypotheses and feasible experimental designs towards identifying biomarkers of neurodegenerative disease by focusing on analytes that remain stable regardless of time of sample collection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0935-1) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%