Antibody based reagents that specifically recognize toxic oligomeric forms of beta-amyloid

Description

Neurodegenerative diseases such as Alzheimer's 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 immunization for Alzheimer's is one promising therapeutic approach, yet current techniques utilize monomeric or fibrillar aggregates of the protein beta-amyloid (Aß), rather than the preferred oligomeric Aß form.

Researchers at Arizona State University have developed a suite of technologies that have the potential to diagnose, immunize, and treat Alzheimer's 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 Aß species. C6 recognizes the toxic, cell-derived oligomeric Aß 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 Aß species that could initiate formation of antibodies to the toxic Aß species of Alzheimer's. Likewise, E1 has potential as a therapeutic and immunization, as it can convert early aggregates into stable non-toxic Aß 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 Alzheimer's and other neurodegenerative diseases (such as Parkinson's) by sampling serum or CSF and recognizing the morphologies of Aß species and other aggregates.

Potential Applications

  • Early diagnosis, immunization, and treatment of Alzheimer's

Benefits and Advantages

  • Specifically recognizes the toxic oligomeric Aß species that cause Alzheimer's
  • Can convert early-stage aggregates into stable non-toxic Aß aggregates before they can aggregate to form the larger, toxic oligomeric Aß form
  • Useful as immunizations to target the toxic Aß species, or to catalyze the formation of stable non-toxic Aß aggregates that do not lead to neuropathy
  • Biosensor can be developed with these reagents to detect and distinguish Alzheimer's, Parkinson's, and other neurodegenerative diseases

For more information about the inventor(s) and their research, please see
Dr. Sierks' directory webpage
Dr. Sierks' laboratory webpage