title: Factors affecting Aβ plasma levels and their utility as biomarkers in ADNI.
abstract: Previous studies of Aβ plasma as a biomarker for Alzheimer's disease (AD) obtained conflicting results. We here included 715 subjects with baseline Aβ(1-40) and Aβ(1-42) plasma measurement (50% with 4 serial annual measurements): 205 cognitively normal controls (CN), 348 patients mild cognitive impairment (MCI) and 162 with AD. We assessed the factors that modified their concentrations and correlated these values with PIB PET, MRI and tau and Aβ(1-42) measures in cerebrospinal fluid (CSF). Association between Aβ and diagnosis (baseline and prospective) was assessed. A number of health conditions were associated with altered concentrations of plasma Aβ. The effect of age differed according to AD stage. Plasma Aβ(1-42) showed mild correlation with other biomarkers of Aβ pathology and were associated with infarctions in MRI. Longitudinal measurements of Aβ(1-40) and Aβ(1-42) plasma levels showed modest value as a prognostic factor for clinical progression. Our longitudinal study of complementary measures of Aβ pathology (PIB, CSF and plasma Aβ) and other biomarkers in a cohort with an extensive neuropsychological battery is significant because it shows that plasma Aβ measurements have limited value for disease classification and modest value as prognostic factors over the 3-year follow-up. However, with longer follow-up, within subject plasma Aβ measurements could be used as a simple and minimally invasive screen to identify those at increased risk for AD. Our study emphasizes the need for a better understanding of the biology and dynamics of plasma Aβ as well as the need for longer term studies to determine the clinical utility of measuring plasma Aβ.
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, HUP, Maloney 3rd (JQT) or 7th (LMS) Floor, 36th and Spruce Streets, Philadelphia, PA, 19104-4283, USA.
authors.forename: Jon B
authors.initials: JB
authors.lastname: Toledo
authors.forename: Hugo
authors.initials: H
authors.lastname: Vanderstichele
authors.forename: Michal
authors.initials: M
authors.lastname: Figurski
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.forename: William
authors.initials: W
authors.lastname: Jagust
authors.forename: Charles
authors.initials: C
authors.lastname: Decarli
authors.forename: Arthur W
authors.initials: AW
authors.lastname: Toga
authors.forename: Estefanía
authors.initials: E
authors.lastname: Toledo
authors.forename: Sharon X
authors.initials: SX
authors.lastname: Xie
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D020520:Brain Infarction / Q000097:blood / Q000175:diagnosis / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging / Q000379:methods*; D011446:Prospective Studies
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers