TTR, Dako, A0002

This is a literature review on the use of the pan-TTR antibody A0002 from DAKO.
A0002 is a robust total TTR detector. It binds both native tetrameric TTR and amyloid aggregated TTR (ATTR) with high sensitivity, making it excellent for IHC staining of both TTR and ATTR in tissues and for pan-TTR detection by Western blotting and IP. It is not amyloid selective so pairing with an amyloid specific antibody is required for distinguishing between TTR and ATTR.
Higaki et al. and Michalon et al. use IHC to show that A0002 labels ATTR positive myocardial deposits that co-localize with Congo red and Thioflavin staining but A0002 also labels native TTR in pancreas and liver.
Michalon et al. show that A0002 detects both tetramers and aggregates of a range of mutant TTR variants with high sensitivity using Western blotting and dot blotting, and that it specifically immunoprecipitates native TTR from human plasma.
The two cited papers describe the discovery of the clinical stage ATTR selective mAbs NI006 and PRX004, respectively.

References:
Higaki et al. Amyloid (2016). Novel Conformation-specific monoclonal antibodies against amyloidogenic forms of transthyretin
Michalon et al. Nature Communications (2021). A human antibody selective for transthyretin amyloid removes cardiac amyloid through phagocytic immune cells