title: A Novel Plasma Based Biomarker of Alzheimer's Disease.
abstract: Specific biomarkers in a readily accessible biological fluid, such as blood, could aid in the identification, characterization, validation, and routine monitoring of Alzheimer's disease (AD) progression. In the current study, levels of the previously described novel cerebrospinal fluid aberrant protein complex composed of prostaglandin-D-synthase (PDS) and transthyretin (TTR) were quantified in plasma by a custom two-probe sandwich ELISA and compared to amyloid-β (Aβ)(1-42) as a standard plasma biomarker of AD. Plasma was analyzed from 140 probable AD subjects, 135 subjects with mild cognitive impairment (MCI), 74 normal control subjects (NC) prior to MCI transition, 23 diseased control (DC) subjects with either frontotemporal dementia or dementia with Lewy bodies, and 182 normal control (NC) subjects who did not progress to MCI or dementia. Levels of Aβ(1-42) were significantly elevated in NC subjects prior to MCI conversion but significantly reduced in probable AD subjects compared to NC subjects. Similarly, levels of the PDS-TTR complex were significantly reduced in both MCI and probable AD subjects compared to NC subjects. Furthermore, levels of Aβ(1-42) and the PDS-TTR complex were not significantly different in DC subjects compared to NC subjects. MMSE scores were weakly but significantly correlated with plasma levels of the PDS-TTR complex and Aβ(1-42). Trail B scores were weakly but significantly correlated with plasma levels of Aβ(1-42). Comparison of receiver operating curves shows the PDS-TTR complex is comparable to Aβ(1-42) in both MCI and probable AD subjects.
authors.affiliation: Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Bradley-Whitman
authors.affiliation: Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, USA.|Department of Epidemiology, University of Kentucky, Lexington, KY, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Abner
authors.affiliation: Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, USA.|University of Kentucky Mass Spectrometry Facility, University of Kentucky, Lexington, KY, USA.|Department of Chemistry, University of Kentucky, Lexington, KY, USA.
authors.forename: Bert C
authors.initials: BC
authors.lastname: Lynn
authors.affiliation: Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, USA.|Department of Chemistry, University of Kentucky, Lexington, KY, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lovell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood*; D016229:Amyloid beta-Peptides / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis; D060825:Cognitive Dysfunction / Q000097:blood; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000097:blood*; D054834:Lipocalins / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000097:blood; D011228:Prealbumin / Q000378:metabolism*; D012372:ROC Curve
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D054834:Lipocalins; D010446:Peptide Fragments; D011228:Prealbumin; C075222:amyloid beta-protein (1-42); D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase
keywords: Alzheimer’s disease; PDS-TTR complex; biomarker; plasma