Evolution of Alzheimer's Disease Cerebrospinal Fluid Biomarkers in Early Parkinson's Disease

David J. Irwin, Janel Fedler, Christopher S. Coffey, Chelsea Caspell-Garcia, Ju Hee Kang, Tanya Simuni, Tatiana Foroud, Arthur W. Toga, Caroline M. Tanner, Karl Kieburtz, Lana M. Chahine, Alyssa Reimer, Samantha Hutten, Daniel Weintraub, Brit Mollenhauer, Douglas R. Galasko, Andrew Siderowf, Kenneth Marek, John Q. Trojanowski, Leslie M. Shaw

Research output: Contribution to journalArticle

Abstract

Objective: We analyzed the longitudinal profile of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers in early Parkinson's disease (PD) compared with healthy controls (HCs) and tested baseline CSF biomarkers for prediction of clinical decline in PD. Methods: Amyloid-β 1 to 42 (Aβ42), total tau (t-tau) and phosphorylated tau (p-tau) at the threonine 181 position were measured using the high-precision Roche Elecsys electrochemiluminescence immunoassay in all available CSF samples from longitudinally studied patients with PD (n = 416) and HCs (n = 192) followed for up to 3 years in the Parkinson's Progression Markers Initiative (PPMI). Longitudinal CSF and clinical data were analyzed with linear-mixed effects models. Results: We found patients with PD had lower CSF t-tau (median = 157.7 pg/mL; range = 80.9–467.0); p-tau (median = 13.4 pg/mL; range = 8.0–40.1), and Aβ42 (median = 846.2 pg/mL; range = 238.8–3,707.0) than HCs at baseline (CSF t-tau median = 173.5 pg/mL; range = 82.0–580.8; p-tau median = 15.4 pg/mL; range = 8.1–73.6; and Aβ42 median = 926.5 pg/mL; range = 239.1–3,297.0; p < 0.05–0.001) and a moderate-to-strong correlation among these biomarkers in both patients with PD and HCs (Rho = 0.50–0.97; p < 0.001). Of the patients with PD, 31.5% had pathologically low levels of CSF Aβ42 at baseline and these patients with PD had lower p-tau levels (median = 10.8 pg/mL; range = 8.0–32.8) compared with 27.7% of HCs with pathologically low CSF Aβ42 (CSF p-tau median = 12.8 pg/mL; range 8.2–73.6; p < 0.03). In longitudinal CSF analysis, we found patients with PD had greater decline in CSF Aβ42 (mean difference = −41.83 pg/mL; p = 0.03) and CSF p-tau (mean difference = −0.38 pg/mL; p = 0.03) at year 3 compared with HCs. Baseline CSF Aβ42 values predicted small but measurable decline on cognitive, autonomic, and motor function in early PD. Interpretation: Our data suggest baseline CSF AD biomarkers may have prognostic value in early PD and that the dynamic change of these markers, although modest over a 3-year period, suggest biomarker profiles in PD may deviate from healthy aging. ANN NEUROL 2020.

Original languageEnglish (US)
JournalAnnals of neurology
DOIs
StateAccepted/In press - 2020

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Irwin, D. J., Fedler, J., Coffey, C. S., Caspell-Garcia, C., Kang, J. H., Simuni, T., Foroud, T., Toga, A. W., Tanner, C. M., Kieburtz, K., Chahine, L. M., Reimer, A., Hutten, S., Weintraub, D., Mollenhauer, B., Galasko, D. R., Siderowf, A., Marek, K., Trojanowski, J. Q., & Shaw, L. M. (Accepted/In press). Evolution of Alzheimer's Disease Cerebrospinal Fluid Biomarkers in Early Parkinson's Disease. Annals of neurology. https://doi.org/10.1002/ana.25811