The Accelerating Medicines Partnership-AD (AMP-AD) project has taken an unbiased, systems-based approach to identify new molecular and cellular targets in AD. The majority of the key driver genes thus far identified encode understudied proteins. Understanding the biology of these proteins, and thus their therapeutic potential, demands high-quality research tools, most notably, specific antibodies for use in multiple applications. Antibodies are indispensable research tools and already there are antibodies available to at least 85% of the human genome, and yet the attention given to generating antibodies has not been matched with an equal effort on antibody validation, leading to serious flaws in the reliability of many of the available reagents. A recent effort funded by the amyotrophic lateral sclerosis (ALS) societies of the USA, Canada and the UK has led to the development of an antibody validation pipeline that has identified high- quality antibody reagents for the major know ALS disease gene. This supplement to the project ?Open systems for AMP-AD target enhancement? (RF1-AG057443-01; PI- Mangravite) will address an important aspect of that project, namely the promise to develop and distribute high-quality reagents for identified targets, including antibodies. Commercial antibodies against fifteen, high-priority targets selected by AMP-AD Investigators, will be subject to the antibody characterization pipeline to identify suitable antibodies for use in all major applications. As for the AMP-AD, the Montreal Neurological Institute, where these studies will be conducted is an Open-Science institute such that all data related to the analysis of the antibodies will be made immediately publicly available, enhancing the pace and quality of AD research. generation of new antibodies.?
AD is a devastating, fatal disease that lacks disease-modifying therapies. To address this, AMP-AD has identified new potential therapeutic targets, yet determining the value of these targets requires their functional analysis, which demands analytical tools including antibodies. The proposed work will use an antibody validation pipeline to identify high-quality antibodies for 15 key AMP-AD targets.