BACKGROUND: Age and sex differences are closely related to the onset of senile systemic amyloidosis (SSA) caused by wild-type (WT) transthyretin (TTR). However, the effects of these differences on the amyloid formation mechanism in familial amyloid polyneuropathy (FAP) caused by variant TTR, have remained unclear. To elucidate age and sex differences in FAP, we investigated biochemical characteristics of amyloid deposits in different tissue sites of FAP by proteomic analysis. METHODS: We used shotgun liquid chromatography/tandem mass spectrometry to analyze the proportions of variant and WT TTR in amyloid deposits in different tissues, such as cardiac, kidney, peripheral nerves, and gastrointestinal tissues, from 23 autopsied FAP cases. RESULTS AND CONCLUSIONS: The analysis revealed a highly significant correlation between the proportion of WT TTR and age at autopsy in cardiac tissues, whereas the analysis indicated no correlation in kidney, peripheral nerves, and gastrointestinal tissues. In addition, we demonstrated age-related significantly increased WT TTR deposits, but not variant TTR deposits, in cardiac tissues of male patients. Taken together, these data suggest that both age and sex differences affect cardiac amyloid formation, mainly derived from WT TTR, in FAP.
BACKGROUND: Age and sex differences are closely related to the onset of senile systemic amyloidosis (SSA) caused by wild-type (WT) transthyretin (TTR). However, the effects of these differences on the amyloid formation mechanism in familial amyloid polyneuropathy (FAP) caused by variant TTR, have remained unclear. To elucidate age and sex differences in FAP, we investigated biochemical characteristics of amyloid deposits in different tissue sites of FAP by proteomic analysis. METHODS: We used shotgun liquid chromatography/tandem mass spectrometry to analyze the proportions of variant and WT TTR in amyloid deposits in different tissues, such as cardiac, kidney, peripheral nerves, and gastrointestinal tissues, from 23 autopsied FAP cases. RESULTS AND CONCLUSIONS: The analysis revealed a highly significant correlation between the proportion of WT TTR and age at autopsy in cardiac tissues, whereas the analysis indicated no correlation in kidney, peripheral nerves, and gastrointestinal tissues. In addition, we demonstrated age-related significantly increased WT TTR deposits, but not variant TTR deposits, in cardiac tissues of male patients. Taken together, these data suggest that both age and sex differences affect cardiac amyloid formation, mainly derived from WT TTR, in FAP.
Authors: Michelle M Hill; Surendra Dasari; Peter Mollee; Giampaolo Merlini; Catherine E Costello; Bouke P C Hazenberg; Martha Grogan; Angela Dispenzieri; Morie A Gertz; Taxiarchis Kourelis; Ellen D McPhail Journal: Mayo Clin Proc Date: 2021-04-09 Impact factor: 11.104
Authors: Hedvig Paulsson Rokke; Nima Sadat Gousheh; Per Westermark; Ole B Suhr; Intissar Anan; Elisabet Ihse; Björn Pilebro; Jonas Wixner Journal: Orphanet J Rare Dis Date: 2020-10-08 Impact factor: 4.123
Authors: Francesca Genova; Simona Nonnis; Elisa Maffioli; Gabriella Tedeschi; Maria Giuseppina Strillacci; Michela Carisetti; Giuseppe Sironi; Francesca Anna Cupaioli; Noemi Di Nanni; Alessandra Mezzelani; Ettore Mosca; Christopher R Helps; Peter A J Leegwater; Laetitia Dorso; Maria Longeri Journal: Sci Rep Date: 2021-04-16 Impact factor: 4.379