CSF levels of oligomeric alpha-synuclein and beta-amyloid as biomarkers for neurodegenerative disease

By Sierks, Michael R.; Chatterjee, Gaurav; McGraw, Claire; Kasturirangan, Srinath; Schulz, Philip & Prasad, Shalini
Published in Integr. Biol. The Royal Society of Chemistry 2011

Abstract

Protein misfolding and aggregation is a critically important feature in many devastating neurodegenerative diseases, therefore characterization of the CSF concentration profiles of selected key forms and morphologies of proteins involved in these diseases, including [small beta]-amyloid (A[small beta]) and [small alpha]-synuclein (a-syn), can be an effective diagnostic assay for these diseases. CSF levels of tau and A[small beta] have been shown to have great promise as biomarkers for Alzheimer ' s disease. However since the onset and progression of many neurodegenerative diseases have been strongly correlated with the presence of soluble oligomeric aggregates of proteins including various A[small beta] and a-syn aggregate species, specific detection and quantification of levels of each of these different toxic protein species in CSF may provide a simple and accurate means to presymptomatically diagnose and distinguish between these diseases. Here we show that the presence of different protein morphologies in human CSF samples can be readily detected using highly selective morphology specific reagents in conjunction with a sensitive electronic biosensor. We further show that these morphology specific reagents can readily distinguish between post-mortem CSF samples from AD, PD and cognitively normal sources. These studies suggest that detection of specific oligomeric aggregate species holds great promise as sensitive biomarkers for neurodegenerative disease.

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