The invention provides methods of detecting transthyretin (TTR) using a capture antibody and a reporter antibody. The capture antibody binds preferentially to misfolded TTR over native tetrameric form of TTR. The capture antibody binds to an epitope within amino acid residues 89-97 or TTR or to an epitope within amino acid residues 101-109 of TTR. 9D5 and 18C5 are examples of suitable capture antibodies. The methods can be used for diagnosing diseases or disorders associated with TTR accumulation or accumulation of TTR deposits (e.g., TTR amyloidosis) and for monitoring the efficacy of TTR therapies, among other applications.