To elucidate the contribution of wild-type transthyretin (TTR) to amyloid polyneuropathy in TTR amyloidosis, we biochemically investigated amyloid fibrils isolated from sciatic nerve of an autopsied patient with TTR Ala25Ser variant and compared the amount of wild-type and variant TTR in the nerve to that in the heart. Amyloid subunit protein from isolated fibrils was solubilized in 6M guanidine HCl and purified by gel filtration chromatography. The relative amounts of variant and wild-type TTR in the purified protein were estimated from the recovered amounts of tryptic peptides with Ser25 or Ala25. Approximately 60% variant and 40% wild-type TTR were found in both the nerve and heart amyloid deposits. Our results indicate that wild-type TTR co-deposits in the peripheral nerves with variant TTR as amyloid fibril, and therefore that progression of amyloid deposition in the peripheral nerves from wild-type TTR may occur after liver transplantation, as has been seen in the heart.