An Alzheimer's Disease-Derived Biomarker Signature Identifies Parkinson's Disease Patients with Dementia

• Published in: PloS one 2016-01, Vol.11 (1), p.e0147319-e0147319
• Main Authors: Berlyand, Yosef, Weintraub, Daniel, Xie, Sharon X, Mellis, Ian A, Doshi, Jimit, Rick, Jacqueline, McBride, Jennifer, Davatzikos, Christos, Shaw, Leslie M, Hurtig, Howard, Trojanowski, John Q, Chen-Plotkin, Alice S
• Format: Article
• Language: English
• Subjects: Aged; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Alzheimers disease; Amyloid beta-Peptides - metabolism; Apolipoprotein E; Apolipoproteins E - genetics; Bioindicators; Biological markers; Biology and Life Sciences; Biomarkers; Biomarkers - metabolism; Brain research; Cerebrospinal fluid; Classifiers; Cluster Analysis; Clustering; Cognition; Cognition & reasoning; Cognitive ability; Cohort Studies; Complications and side effects; Consent; Correlation; Correlation analysis; Correlation coefficient; Correlation coefficients; Cross-Sectional Studies; Dementia; Dementia - complications; Dementia - diagnosis; Dementia disorders; Diagnosis; Female; Genetic aspects; Genotype; Genotypes; Humans; Laboratories; Logistic Models; Male; Medicine; Medicine and Health Sciences; Middle Aged; Movement disorders; Neurodegenerative diseases; Neurology; Parkinson disease; Parkinson Disease - complications; Parkinson Disease - diagnosis; Parkinson's disease; Parkinsons disease; Pathology; Patients; Peptide Fragments - metabolism; Phosphorylation; Physiological aspects; Risk factors; Social Sciences; Tau protein; tau Proteins - cerebrospinal fluid
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0147319

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.