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Basic Science and Pathogenesis.

Riham Ayoubi1, Aled M Edwards2, Peter S McPherson1

  • 1Montreal Neurological Institute-McGill University, Montreal, QC, Canada.

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Summary
This summary is machine-generated.

High-quality antibodies are crucial for Alzheimer's disease (AD) research beyond the main genes. The TREAT-AD program and YCharOS initiative are developing and validating reliable tools for studying AD-associated proteins, enabling new discoveries.

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Area of Science:

  • Neuroscience
  • Genetics
  • Biotechnology

Background:

  • Alzheimer's disease (AD) research is limited by a narrow focus on a few genes, neglecting numerous other risk factors.
  • A significant hurdle in studying AD is the lack of selective and renewable antibodies for many associated proteins.
  • The Target Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT-AD) program aims to address this by developing essential research tools for understudied AD targets.

Purpose of the Study:

  • To characterize antibodies for Alzheimer's disease (AD) targets using a standardized, open-science approach.
  • To identify and validate reliable research tools for studying a broader range of AD-associated proteins.
  • To enable hypothesis testing and advance understanding of AD etiology through improved molecular investigations.

Main Methods:

  • The Antibody Characterization through Open Science (YCharOS) initiative employs knockout cell lines for side-by-side antibody validation.
  • Antibodies are tested for performance in Western blot, immunoprecipitation, and immunofluorescence assays.
  • Results are openly disseminated via the AD Knowledge Portal, promoting transparency and accessibility.

Main Results:

  • 441 antibodies targeting 41 prioritized AD proteins have been characterized, revealing frequent issues with specificity in commonly used antibodies.
  • Selective and renewable antibodies were found for 90% of TREAT-AD targets, including newly generated and rarely used options.
  • The TREAT-AD program generated recombinant antibodies for proteins like SMOC1, demonstrating superior selectivity; knockout-validated antibodies confirmed upregulation of CD44, Moesin, sFRP-1, and Midkine in AD models.

Conclusions:

  • YCharOS has established robust antibody characterization standards that meet funding and journal requirements.
  • The initiative is dedicated to identifying and providing reliable, accessible tools essential for advancing Alzheimer's disease research.