Evolution of Alzheimer's Disease Cerebrospinal Fluid Biomarkers in Early Parkinson's Disease
Year: 2020
Type: article
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;88:574–587
Source: Annals of Neurology
DOI: 10.1002/ana.25811
Authors: 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, The Parkinson's Progression Marker Initiative
Institutions: University of Pennsylvania, University of Iowa, Inha University, Northwestern University, Indiana University Indianapolis, Indiana University School of Medicine, University of Southern California, University of California, San Francisco, University of Rochester Medicine, University of Rochester, University of Pittsburgh, Michael J. Fox Foundation, Philadelphia VA Medical Center, Universitätsmedizin Göttingen, Paracelsus Elena Klinik Kassel, University of San Diego, Institute for Neurodegenerative Disorders
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,000
Funders: Michael J. Fox Foundation for Parkinson's Research, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, GlaxoSmithKline, Sanofi, Biogen, Teva Pharmaceutical Industries, Celgene, University of Pennsylvania, F. Hoffmann-La Roche, Voyager Therapeutics, Servier, H. Lundbeck A/S, National Institutes of Health, Genentech, Allergan, Sanofi Genzyme, Avid Radiopharmaceuticals, National Institute on Aging, National Institute of Neurological Disorders and Stroke
OpenAlex ID: W3034879277