title: An Alzheimer's Disease-Derived Biomarker Signature Identifies Parkinson's Disease Patients with Dementia.
abstract: Biomarkers from multiple modalities have been shown to correlate with cognition in Parkinson's disease (PD) and in Alzheimer's disease (AD). However, the relationships of these markers with each other, and the use of multiple markers in concert to predict an outcome of interest, are areas that are much less explored. Our objectives in this study were (1) to evaluate relationships among 17 biomarkers previously reported to associate with cognition in PD or AD and (2) to test performance of a five-biomarker classifier trained to recognize AD in identifying PD with dementia (PDD). To do this, we evaluated a cross-sectional cohort of PD patients (n = 75) across a spectrum of cognitive abilities. All PD participants had 17 baseline biomarkers from clinical, genetic, biochemical, and imaging modalities measured, and correlations among biomarkers were assessed by Spearman's rho and by hierarchical clustering. We found that internal correlation among all 17 candidate biomarkers was modest, showing a maximum pairwise correlation coefficient of 0.51. However, a five-marker subset panel derived from AD (CSF total tau, CSF phosphorylated tau, CSF amyloid beta 42, APOE genotype, and SPARE-AD imaging score) discriminated cognitively normal PD patients vs. PDD patients with 80% accuracy, when employed in a classifier originally trained to recognize AD. Thus, an AD-derived biomarker signature may identify PDD patients with moderately high accuracy, suggesting mechanisms shared with AD in some PDD patients. Based on five measures readily obtained during life, this AD-derived signature may prove useful in identifying PDD patients most likely to respond to AD-based crossover therapies.
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Yosef
authors.initials: Y
authors.lastname: Berlyand
authors.affiliation: Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weintraub
authors.affiliation: Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Sharon X
authors.initials: SX
authors.lastname: Xie
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Mellis
authors.affiliation: Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jimit
authors.initials: J
authors.lastname: Doshi
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Rick
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.|Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: McBride
authors.affiliation: Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Christos
authors.initials: C
authors.lastname: Davatzikos
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Howard
authors.initials: H
authors.lastname: Hurtig
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.|Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Alice S
authors.initials: AS
authors.lastname: Chen-Plotkin
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism*; D016000:Cluster Analysis; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003704:Dementia / Q000150:complications / Q000175:diagnosis*; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000175:diagnosis*; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
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