Appropriateness of Applying Cerebrospinal Fluid Biomarker Cutoffs from Alzheimer’s Disease to Parkinson’s Disease

Article type: Research Article

Authors: Weinshel, Sarah^{a; b} | Irwin, David J.^c | Zhang, Panpan^b | Weintraub, Daniel^{c; d; e} | Shaw, Leslie M.^f | Siderowf, Andrew ^c | Xie, Sharon X.^{b; *}

Affiliations: [a] Swarthmore College, Swarthmore, PA, USA | [b] Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA | [c] Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA | [d] Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA | [e] Michael J. Crescenz VA Medical Center, Parkinson’s Disease Research, Education, and Clinical Center, Philadelphia, PA, USA | [f] Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

Correspondence: [*] Correspondence to: Sharon X. Xie, PhD, Professor of Biostatistics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA 19104-6021, USA. Tel.: +1 215 573 3867; E-mail: [email protected].

Abstract: Background:While cutoffs for abnormal levels of the cerebrospinal fluid (CSF) biomarkers amyloid-β 1-42 (Aβ142), total tau (t-tau), phosphorylated tau (p-tau), and the ratios of t-tau/Aβ142 and p-tau/Aβ142, have been established in Alzheimer’s disease (AD), biologically relevant cutoffs have not been studied extensively in Parkinson’s disease (PD). Objective:Assess the suitability and diagnostic accuracy of established AD-derived CSF biomarker cutoffs in the PD population. Methods:Baseline and longitudinal data on CSF biomarkers, cognitive diagnoses, and PET amyloid imaging in 423 newly diagnosed patients with PD from the Parkinson’s Progression Markers Initiative (PPMI) cohort were used to evaluate established AD biomarker cutoffs compared with optimal cutoffs derived from the PPMI cohort. Results:Using PET amyloid imaging as the gold standard for AD pathology, the optimal cutoff of Aβ142 was higher than the AD cutoff, the optimal cutoffs of t-tau/Aβ142 and p-tau/Aβ142 were lower than the AD cutoffs, and their confidence intervals (CIs) did not overlap with the AD cutoffs. Optimal cutoffs for t-tau and p-tau to predict cognitive impairment were significantly lower than the AD cutoffs, and their CIs did not overlap with the AD cutoffs. Conclusion:Optimal cutoffs for the PPMI cohort for Aβ142, t-tau/Aβ142, and p-tau/Aβ142 to predict amyloid-PET positivity and for t-tau and p-tau to predict cognitive impairment differ significantly from cutoffs derived from AD populations. The presence of additional pathologies such as alpha-synuclein in PD may lead to disease-specific CSF biomarker characteristics.

Keywords: Parkinson’s disease, Alzheimer’s disease, cerebrospinal fluid, cutoff, PET

DOI: 10.3233/JPD-212989

Journal: Journal of Parkinson's Disease, vol. 12, no. 4, pp. 1155-1167, 2022