A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors

Abstract

The amyloid proteins isolated from neuritic plaques and the cerebrovasculature of Alzheimer's disease are self-aggregating moieties termed A4 protein1 and βprotein2,3, respectively. A putative A4 amyloid precursor (herein termed A4695) has been characterized by analysis of a human brain complementary DNA4. We report here the sequence of a closely related amyloid cDNA, A4751,distinguished from A4695 by the presence of a 168 base-pair (bp) sequence which adds 57 amino acids to, and removes one residue from, the predicted A4 695protein. The peptide predicted from this insert is very similar to the Kunitz family of serine proteinase inhibitors. The two A4-specific messenger RNAs are differentially expressed: in a limited survey, A4751 mRNA appears to be ubiquitous, whereas A4695 mRNA has a restricted pattern of expression which includes cells from neuronal tissue. These data may have significant implications for understanding amyloid deposition in Alzheimer's disease.