Severe amyloid deposition in mammary glands of familial amyloid polyneuropathy patients

Abstract

Clinical pictures of familial amyloid polyneuropathy (FAP) vary considerably, perhaps because of the many gene mutations of transthyretin (TTR), but even in patients having the most common mutation of TTR (the substitution of methionine for valine at position 30 (ATTRVal30Met)), the age of onset ranges from the late 20s to the early 60s. Although genetic anticipation has been considered to play a role in producing this wide range of ages of onset, the precise pathogenesis is incompletely understood. It has been experimentally shown that murine systemic AA and AApoAII amyloidoses can be transmitted by ingestion of amyloid fibrils themselves or amyloid-like pathological agents. In this study, we examined biopsied mammary glands obtained from three female ATTRVal30Met FAP patients who were of gestation age. Amyloid deposition was commonly seen in the glands and, in the two patients with apparent FAP symptoms, heavy deposits of amyloid surrounded many lactiferous alveoli and ducts, where some deposits of amyloid actually faced the central lumens. These findings raise the possibility that milk from FAP mothers contains ATTR-derived amyloid fibrils and/or fragments, which might be causally related to the development of genetic anticipation in this disease.

Keywords:

• Amyloid
• familial amyloid polyneuropathy
• transmission
• anticipation
• mammary gland

Abbreviations
FAP	=	familial amyloid polyneuropathy;
TTR	=	transthyretin

Abbreviations
FAP	=	familial amyloid polyneuropathy;
TTR	=	transthyretin