Transthyretin gene in Alzheimer's disease patients

Amyloid beta (Abeta) is known to be the main component of Alzheimer's disease (AD) senile plaques. A homologous peptide is a normal component of biological fluids and is called soluble Abeta (sAbeta). Synthetic peptides homologous to Abeta form amyloid-like fibrils in vitro. This fibril formation can be inhibited by normal human cerebrospinal fluid (CSF) [Wisniewski et al., Ann. Neurol. 34 (1993)]. Furthermore, it has been proposed that normal transthyretin (TTR), which is a component of CSF, can itself bind sAbeta, preventing amyloid fibril formation, and that variants of TTR could be associated with AD [Schwarzman et al., Proc. Natl. Acad. Sci. USA, 91 (1994)]. Because of this possible association, we screened for TTR mutations from 47 sporadic and 19 early-onset familial AD patients using single strand conformation polymorphism analysis. Our results show no correlation between TTR variants and Alzheimer's disease in this group of patients.