Tau protein fibrils are determined to be a pathological hallmark of several neurodegenerative disorders such as Alzheimer's disease (AD), dementia, and other neurodegenerative diseases termed tauopathies [1]. Tau by itself cannot undergo aggregation, but in the presence of an inducer can form the fibrils neurofibrillary tangles and paired helical filaments, among other structures. The interest in therapeutic targeting tau pathology has sparked the drug design and development. Lately, immunotherapies in mouse models have succeeded in reducing aggregate levels and promoting aggregate clearance [2]. Typical immunotherapies are mixtures of complex antibodies which makes the identification of the inhibitor antibody challenging. To gain insight into the site-specific targeting of tau via antibodies, we have investigated four monoclonal and polyclonal antibodies and commercially available immunotherapeutic formulation. The antibodies used were targeting the specific tau domains: N-terminal, C-terminal, or R (R1-R4) domains.Two different approaches were used: 1) prevention of tau aggregation and 2) dissolution of tau aggregates in the presence of antibodies. The addition of specific antibodies to the reaction of tau441, longest tau isoform, and arachidonic disrupted the aggregation process. For dissolution studies, preformed tau aggregates were treated with antibodies. The transmission electron microscopy (TEM) was used to confirm tau aggregates, monitor tau aggregation, detect aggregation inhibition and aggregate dissolution.

Tau protein aggregation inhibition and aggregate dissolution via immunotherapies

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.