Familial amyloidotic polyneuropathy (ATTR Val30Met) with widespread cerebral amyloid angiopathy and lethal cerebral...

We report an autopsy case of familial amyloidotic polyneuropathy (FAP) with cerebral hemorrhage. A 38-year-old woman with a typical FAP pedigree started developing severe diarrhea and sensori-motor polyneuropathy at the age of 28 years; autonomic nervous system, heart and renal dysfunction manifested themselves in the following years. Genetic analysis revealed a single amino acid substitution at codon 30 of transthyretin (ATTR Val30Met). Ten years after her initial symptoms, the patient died of a sudden convulsive attack and respiratory failure. Autopsy revealed lethal cerebral hemorrhages and uremic lungs. Histochemical and immunohistochemical analyses revealed TTR-derived amyloid protein in every tissue examined, particularly in glomeruli and peripheral vessels. Severe meningo-cerebrovascular amyloidosis was also detected. Because uremia causes oxidative damage to the vascular system and amyloid formation is closely associated with oxidative stress, it is possible that uremic endothelial damage facilitated an unusual cerebral amyloid deposition. In typical FAP (ATTR Val30Met), cerebral amyloid angiopathy does not usually have clinical manifestations. However, cerebral amyloid angiopathy should be considered to explain FAP symptoms when some risk factors such as uremic vascular damage are accompanying features.