Antibody based reagent that specifically recognizes toxic oligomeric form of beta-amyloid

Michael Sierks (Inventor)

Research output: Patent

Abstract

Neurodegenerative diseases such as Alzheimers are affecting an increasing number, with annual new diagnoses approaching one-half million; and total cost, $150 billion. Early diagnosis and treatment are important for optimal outcomes, yet there is currently no test to detect such diseases in their early, asymptomatic stages. Active immuniza-tion for Alzheimers is one promising therapeutic approach, yet current techniques utilize monomeric or fibrillar aggregates of the protein beta-amyloid (A), rather than the preferred oligomeric A form. Researchers at Arizona State University have developed a suite of technologies that have the potential to diagnose, immunize, and treat Alzheimers Disease in its early, asymptomatic stage, when such treatments are likely to be most effective. Specifically, they have isolated antibody-based reagents (C6 and E1) that catalyze formation of two different oligomeric A species. C6 recognizes the toxic, cell-derived oligomeric A with high specificity. This has been demonstrated in vivo with a trans-genic mouse model and in vitro with extracted human brain tissue. C6 thus, has potential in immunizations where it could catalyze formation of oligomeric A species that could initiate formation of antibodies to the toxic A species of Alzheimers. Likewise, E1 has potential as a therapeutic and immunization, as it can convert early aggregates into stable non-toxic A aggregates, or initiate generation of antibodies that could themselves effect the conversion. Finally, the researchers have also developed an electrochemical impedance biosensor utilizing C6 and E1. This sensor can detect early-stage Alzheimers and other neurodegenerative diseases (such as Parkinsons) by sampling serum or CSF and recognizing the morphologies of A species and other aggregates. Potential Applications Early diagnosis, immunization, and treatment of Alzheimers Benefits and Advantages Specifically recognizes the toxic oligomeric A species that cause Alzheimers Can convert early-stage aggregates into stable non-toxic A aggregates before they can aggregate to form the larger, toxic oligomeric A form Useful as immunizations to target the toxic A species, or to catalyze the formation of stable non-toxic A aggregates that do not lead to neuropathy Biosensor can be developed with these reagents to detect and distinguish Alzheimers, Parkinsons, and other neurodegenerative diseases Dowload Original PDF For more information about the inventor(s) and their research, please see Dr. Sierks' directory webpage Dr. Sierks' laboratory webpage
Original languageEnglish (US)
Publication statusPublished - Jun 7 2010

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