A multivariate predictive modeling approach reveals a novel CSF peptide signature for both Alzheimer's Disease state classification and for predicting future disease progression

• Published in: PloS one Vol. 12; no. 8; p. e0182098
• Main Authors: Llano, Daniel A, Bundela, Saurabh, Mudar, Raksha A, Devanarayan, Viswanath
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03-08-2017; Public Library of Science (PLoS)
• Subjects: Aged; Aged, 80 and over; Algorithms; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - pathology; Alzheimer's disease; Amino Acid Sequence; Amyloid beta-Peptides - cerebrospinal fluid; Analysis; Apolipoprotein E; Apolipoproteins E - cerebrospinal fluid; Area Under Curve; Biological markers; Biology and Life Sciences; Biomarkers; Brain research; Case-Control Studies; Cerebrospinal fluid; Classification; Cognitive ability; Databases, Factual; Dementia; Disease control; Disease Progression; Ethics; Fatty acid-binding protein; Fatty acids; Female; Heart fatty acid-binding protein; Hospitals; Human subjects; Humans; Hypotheses; Identification; Male; Mass spectrometry; Medical imaging; Medicine; Medicine and Health Sciences; Metabolism; Models, Theoretical; Multivariate Analysis; Neurodegenerative diseases; Neuroimaging; Neurology; NMR; Nuclear magnetic resonance; Pentraxins; Peptide Fragments - cerebrospinal fluid; Peptides; Proteins; Proteomics; Review boards; ROC Curve; Science Policy; Scientific imaging; Severity of Illness Index; Signatures; Studies; Tau protein; tau Proteins - cerebrospinal fluid; β-Amyloid; United States > US; North Chicago Illinois
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0182098

To determine if a multi-analyte cerebrospinal fluid (CSF) peptide signature can be used to differentiate Alzheimer's Disease (AD) and normal aged controls (NL), and to determine if this signature can also predict progression from mild cognitive impairment (MCI) to AD, analysis of CSF samples was done on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. The profiles of 320 peptides from baseline CSF samples of 287 subjects over a 3-6 year period were analyzed. As expected, the peptide most able to differentiate between AD vs. NL was found to be Apolipoprotein E. Other peptides, some of which are not classically associated with AD, such as heart fatty acid binding protein, and the neuronal pentraxin receptor, also differentiated disease states. A sixteen-analyte signature was identified which differentiated AD vs. NL with an area under the receiver operating characteristic curve of 0.89, which was better than any combination of amyloid beta (1-42), tau, and phospho-181 tau. This same signature, when applied to a new and independent data set, also strongly predicted both probability and rate of future progression of MCI subjects to AD, better than traditional markers. These data suggest that multivariate peptide signatures from CSF predict MCI to AD progression, and point to potentially new roles for certain proteins not typically associated with AD.