QUANTIFICATION OF SERUM AND CEREBROSPINAL-FLUID GELSOLIN IN FAMILIAL AMYLOIDOSIS, FINNISH TYPE (AGEL)

Familial amyloidosis, Finnish type (FAF) or AGel is an autosomal domin ant systemic amyloidosis, characteristic symptoms of which are progres sive polyneuropathy and corneal lattice dystrophy. The amyloid in FAF patients consists of peptides of an actin modulating protein, gelsolin , with the substitution of Asn or of Tyr for Asp(187). We developed a novel competitive radioimmunoassay for gelsolin quantification in seru m and CSF. The serum gelsolin concentration in our patient material wa s significantly higher (248 mu g/ml) than in the controls (179 mu g/ml ) (P=0.0012). The serum gelsolin levels in patients correlated with ag e (P=0.0001), whereas no age-dependency was observed in the control gr oup. The mean CSF gelsolin concentration in patients below the age of 50 was lower (7.1 mu g/ml) than in controls (10.8 mu g/ml), but increa sed with age in the patient group (P=0.014), as did the total CSF prot ein (P=0.015). Immunoblotting with antibodies to gelsolin revealed one extra fragment of 60 kDA in the serum and two extra fragments of 60-8 5 KDa in the CSF of the patients These findings suggest that the metab olism of gelsolin is altered in FAF. The novel RIA method presented he re can serve as a valuable tool in future analyses aimed at monitoring the gelsolin level in vitro or in vivo.