MP0029:Vattipalli:Monitoring CSF Levels of oligomeric alpha-synuclein and beta-amyloid as Biomarkers for neurodegenerative disease

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 Krishna Vattipalli1, Savindra Brandigampala2, Claire McGraw3, Michael Sierks3, Shalini Prasad1,*
1Bioengineering Department, Erik Jonsson School of Engineering, University of Texas at Dallas, Richardson, TX
2Department of Electrical Engineering and Computer Science, Wichita State University, Wichita, KS
3School of Mechanical, Aerospace, Chemical and Materials Engineering, Arizona State University

Neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) will affect an increasing number of people as our population ages. For AD alone, over 5 million Americans currently are living with the disease, with nearly half a million new cases expected each year with total yearly economic costs of over $170 billion. Diagnosis of these diseases is challenging as other neurodegenerative diseases such as Lewy are often classified as having Mild-Cognitive Impairment (MCI), a term describes early, nondisabling cognitive disorders.

Although MCI describes a transitional state between normal Body Dementia (LBD), frontotemporal dementia and vascular dementia may share similar symptoms, but have different mechanisms and pathology. Patients in early stages of dementia aging and dementia, not all MCI cases progress to dementia. Pathological changes associated with these different dementias have been shown to occur long before symptoms are evident, suggesting that an appropriate set of biomarkers would have great promise to study toxic mechanisms and pathways in these different diseases and to facilitate early diagnoses.

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 beta-amyloid (Aß) and α-synuclein (a-syn), can be an effective diagnostic assay for these diseases. CSF levels of tau and Aß 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 Aß 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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