کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5623076 | 1406199 | 2013 | 14 صفحه PDF | دانلود رایگان |
BackgroundSoluble oligomers of amyloid Ã-protein (AÃ) have been increasingly linked to synaptic dysfunction, tau alteration, and neuritic dystrophy in Alzheimer's disease (AD) and mouse models. There is a great need for assays that quantify AÃ oligomers with high specificity and sensitivity.MethodsWe designed and validated two oligomer-specific (o-) enzyme-linked immunoassays (ELISAs) using either an AÃ aggregate-selective monoclonal for capture and a monoclonal to the free N-terminus for detection, or the latter antibody for both capture and detection.ResultsThe o-ELISAs specifically quantified pure oligomers of synthetic AÃ with sizes from dimers up to much larger assemblies and over a wide dynamic range of concentrations, whereas AÃ monomers were undetectable. Natural AÃ oligomers of similarly wide size and concentration ranges were measured in extracts of AD and control brains, revealing >1000-fold higher concentrations of AÃ oligomers than monomers in the soluble fraction of AD cortex. The assays quantified the age-related rise in oligomers in hAPP transgenic mice. Unexpectedly, none of 90 human cerebrospinal fluid (CSF) samples gave a specific signal in either o-ELISA.ConclusionsThese new o-ELISAs with rigorously confirmed specificity can quantify oligomer burden in human and mouse brains for diagnostic and mechanistic studies and for AD biomarker development. However, our data raise the likelihood that the hydrophobicity of AÃ oligomers makes them very low in number or absent in aqueous CSF.
Journal: Alzheimer's & Dementia - Volume 9, Issue 2, March 2013, Pages 99-112