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01.10.2011 | Original Paper

Factors affecting Aβ plasma levels and their utility as biomarkers in ADNI

verfasst von: Jon B. Toledo, Hugo Vanderstichele, Michal Figurski, Paul S. Aisen, Ronald C. Petersen, Michael W. Weiner, Clifford R. Jack Jr, William Jagust, Charles Decarli, Arthur W. Toga, Estefanía Toledo, Sharon X. Xie, Virginia M.-Y. Lee, John Q. Trojanowski, Leslie M. Shaw

Erschienen in: Acta Neuropathologica | Ausgabe 4/2011

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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.

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Titel: Factors affecting Aβ plasma levels and their utility as biomarkers in ADNI
verfasst von: Jon B. Toledo
Hugo Vanderstichele
Michal Figurski
Paul S. Aisen
Ronald C. Petersen
Michael W. Weiner
Clifford R. Jack Jr
William Jagust
Charles Decarli
Arthur W. Toga
Estefanía Toledo
Sharon X. Xie
Virginia M.-Y. Lee
John Q. Trojanowski
Leslie M. Shaw
Publikationsdatum: 01.10.2011
Verlag: Springer-Verlag
Erschienen in: Acta Neuropathologica / Ausgabe 4/2011
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-011-0861-8

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