Advanced glycation end product in familial amyloidotic polyneuropathy (FAP)

Objectives. Advanced glycation end products (AGE) are present in amyloid de posits in beta(2)-microglobulin amyloidosis, and it has been postulated tha t glycation of beta(2)-microglobulin may be involved in fibril formation. T he aim of this paper was to ascertain whether AGE occur in amyloid deposits in familial amyloidotic polyneuropathy (FAP). Setting. Department of Medicine, Umea University Hospital and First Departm ent of Internal Medicine, Kumamoto University School of Medicine. Design. The presence of AGE was sought immunohistochemically and biochemica lly in amyloid-rich tissues from patients with FAP. Subjects. Biopsy specimens from nine patients and 10 controls were used for the immunohistochemical analysis. For amyloid preparation, vitreous sample s from three FAP patients were used. Results. Immunohistochemical studies using a polyclonal anti-AGE antibody r evealed positive immunoreactivity in intestinal materials, but the pattern of reactivity was unevenly distributed; it was often present in the border of amyloid deposits, or surrounding them. Non-amyloid associated immunoreac tivity was also observed in a few regions of the specimens, although the AG E-positive structures were situated in areas containing amyloid deposits. W estern blotting of purified amyloid from the vitreous body of FAP patients revealed a significant association of AGE with amyloid fibrils. Conclusions. The immunoreactivity for the AGE antibody suggests that AGE ma y be involved in fibril formation in FAP.