C-Terminal Fragments of α- and β-Tubulin Form Amyloid Fibrilsin Vitroand Associate with Amyloid Deposits of Familial Cerebral Amyloid Angiopathy, British Type

Abstract

Familial amyloidosis, British type, is an autosomal dominant disease characterized by progressive dementia, spastic paralysis and ataxia. The identity of the accumulating amyliod is not known, thus preventing the definitive classification of the disease. Biochemical methods were used to characterize the nature of the amyloid deposits from the brain tissue of one individual who died with the 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 GYLTVAAVFR, which are all tryptic fragments of the C-termini of human tubulin subunits α and β. Synthetic peptides based on the sequences of these fragments formed amyloid fibrilsin vitrofitting the characteristic definition of amyloid. These findings suggest that the C-terminal fragments of both α- and β-tubulin are closely associated to the amyloid deposits of familial amyloidsosis, British type.