Codeposition of apolipoprotein A-IV and transthyretin in senile systemic (ATTR) amyloidosis

Protein material was extracted from amyloid-rich sections of formalin-fixed and paraffin-embedded heart tissue from an individual with senile systemic amyloidosis, known to contain wild-type transthyretin as major amyloid fib ril protein. Amino acid sequence analysis of tryptic peptides of this mater ial revealed in addition to transthyretin sequences, also amino acid sequen ce corresponding to an N-terminal fragment of apolipoprotein A-IV. In immun ohistochemistry, an antiserum to a synthetic apolipoprotein A-IV peptide la beled amyloid specifically. This peptide formed spontaneously amyloid-like fibrils in vitro and enhanced fibril formation from wild-type transthyretin . We conclude that several apolipoproteins, including apolipoprotein A-IV, may be important minor amyloid constituents, promoting fibril formation. (C ) 2001 Academic Press.