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; Parkinson's Progression Marker Initiative

doi:10.1002/ana.25811

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

Journal article

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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, …

Annals of neurology, Vol.88(3), pp.574-587

09/2020

DOI: 10.1002/ana.25811

PMCID: PMC7497251

PMID: 32542885

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Abstract

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. Amyloid-β 1 to 42 (Aβ ), 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. 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 Aβ (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 Aβ 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 Aβ 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 Aβ (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 Aβ (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 Aβ values predicted small but measurable decline on cognitive, autonomic, and motor function in early PD. 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.

Aged

Alzheimer Disease - cerebrospinal fluid

Amyloid beta-Peptides - cerebrospinal fluid

Biomarkers - cerebrospinal fluid

Disease Progression

Female

Humans

Longitudinal Studies

Male

Middle Aged

Parkinson Disease

Prospective Studies

tau Proteins - cerebrospinal fluid

Details

Title: Subtitle: Evolution of Alzheimer's Disease Cerebrospinal Fluid Biomarkers in Early Parkinson's Disease
Creators: David J Irwin - Department of Neurology, School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
Janel Fedler - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA
Christopher S Coffey - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA
Chelsea Caspell-Garcia - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA
Ju Hee Kang - Department of Pharmacology & Clinical Pharmacology, Inha University, Incheon, South Korea
Tanya Simuni - Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
Tatiana Foroud - Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, USA
Arthur W Toga - Laboratory of Neuro Imaging, University of Southern California, Los Angeles, CA, USA
Caroline M Tanner - Department of Neurology, University of California San Francisco, San Francisco, CA, USA
Karl Kieburtz - Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA
Lana M Chahine - Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA
Alyssa Reimer - The Michael J. Fox Foundation, New York, NY, USA
Samantha Hutten - The Michael J. Fox Foundation, New York, NY, USA
Daniel Weintraub - Michael J. Crescenz VA Medical Center, Parkinson's Disease Research, Education, and Clinical Center, Philadelphia, PA, USA
Brit Mollenhauer - Department of Neurology, University Medical Center, Göttingen Paracelsus-Elena-Klinik, Kassel, Germany
Douglas R Galasko - Department of Neurology, University of San Diego, San Diego, CA, USA
Andrew Siderowf - Department of Neurology, School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
Kenneth Marek - Institute for Neurodegenerative Disorders, New Haven, CT, USA
John Q Trojanowski - Center for Neurodegenerative Disease Research, School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
Leslie M Shaw - Department of Pathology and Laboratory Medicine, School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
Parkinson's Progression Marker Initiative
Resource Type: Journal article
Publication Details: Annals of neurology, Vol.88(3), pp.574-587
DOI: 10.1002/ana.25811
PMID: 32542885
PMCID: PMC7497251
NLM abbreviation: Ann Neurol
ISSN: 0364-5134
eISSN: 1531-8249
Grant note: K23 NS088341 / NINDS NIH HHS U19 AG062418 / NIA NIH HHS P30 AG010124 / NIA NIH HHS
Language: English
Date published: 09/2020
Academic Unit: Biostatistics
Record Identifier: 9984214846602771

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