C-terminal fragments of alpha- and beta-tubulin form amyloid fibrils in vitro and associate with amyloid deposits of familiar cerebral amyloid angiopathy, British type

Familial amyloidosis, British type, is an autosomal dominant disease characterized by progressive dementia, spastic paralysis and ataxia. The identity of the accumulating amyloid is not known, thus preventing the definitive classification of the disease. Biochemical methods were used to characterize the nature of the amyloid deposits form the brain tissue of one individual who died with this disease. The purified tissue material was subjected to trypsin digestion and subsequent N-terminal sequence analysis. Major tryptic fragments yielded the sequences VGINYQPPTVVPGGDLAK. FDLMYAK, GLTVPEL and GYLTVAAVER, which are all tryptic fragments of the C-termini of human tubulin subunits alpha and beta. Synthetic peptides based on the sequences of these fragments formed amyloid fibrils in vitro, fitting the characteristic definition of amyloid. These findings suggest that the C-terminal fragments of both, alpha- and beta-tubulin are closely associated to the amyloid deposits of familial amyloidosis, British type. (C) 1996 Academic Press Inc.