title: Peripheral α-defensins 1 and 2 are elevated in Alzheimer's disease.
abstract: Biomarkers enabling the preclinical identification of Alzheimer's disease (AD) remain one of the major unmet challenges in the field. The blood cellular fractions offer a viable alternative to current cerebrospinal fluid and neuroimaging modalities. The current study aimed to replicate our earlier reports of altered binding within the AD-affected blood cellular fraction to copper-loaded immobilized metal affinity capture (IMAC) arrays. IMAC and anti-amyloid-β (Aβ) antibody arrays coupled with mass spectrometry were used to analyze blood samples collected from 218 participants from within the AIBL Study of Aging. Peripheral Aβ was fragile and prone to degradation in the AIBL samples, even when stored at -80°C. IMAC analysis of the AIBL samples lead to the isolation and identification of alpha-defensins 1 and 2 at elevated levels in the AD periphery, validating earlier findings. Alpha-defensins 1 and 2 were elevated in AD patients indicating that an inflammatory phenotype is present in the AD periphery; however, peripheral Aβ levels are required to supplement their prognostic power.
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia The Neuroproteomics Platform, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Watt
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia The Neuroproteomics Platform, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia.
authors.forename: Keyla A
authors.initials: KA
authors.lastname: Perez
authors.affiliation: Mass Spectrometry and Proteomics Facility, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia.
authors.forename: Ching-Seng
authors.initials: CS
authors.lastname: Ang
authors.affiliation: Mass Spectrometry and Proteomics Facility, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: O'Donnell
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Rembach
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia.
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Pertile
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Rumble
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia.
authors.forename: Brett O
authors.initials: BO
authors.lastname: Trounson
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Fowler
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia.
authors.forename: Noel G
authors.initials: NG
authors.lastname: Faux
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, Australia.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia Department of Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia The Neuroproteomics Platform, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Barnham
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D018709:Statistics, Nonparametric; D023084:alpha-Defensins / Q000097:blood*
chemical_list: D001057:Apolipoproteins E; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; C406416:human neutrophil peptide 2
keywords: Alzheimer's disease; amyloid-β; biomarkers; blood; inflammation; mass spectrometry; α-defensins