This study reports the molecular cloning of a cDNA encoding an unrecognized component of amyloid in Alzheimer's disease (AD). The researchers identified two unknown peptides, X and Y, in an amyloid preparation, which were tentatively named NAC (non-Aβ component of AD amyloid) and its precursor NACP. NAC is a 35-amino acid peptide with a strong tendency to form β-structures, suggesting its association with amyloid fibrils. The full-length cDNA encoding NACP was isolated, and it encodes a 140-amino-acid protein. NACP is detected as a 19,000 kDa protein in brain homogenates and comigrates with bacterially synthesized NACP. NACP mRNA is predominantly expressed in the brain but is also present in low concentrations in other tissues, except the liver. The findings suggest that NAC may play a role in the formation of amyloid in AD by promoting the conformational change of soluble Aβ into insoluble amyloid.This study reports the molecular cloning of a cDNA encoding an unrecognized component of amyloid in Alzheimer's disease (AD). The researchers identified two unknown peptides, X and Y, in an amyloid preparation, which were tentatively named NAC (non-Aβ component of AD amyloid) and its precursor NACP. NAC is a 35-amino acid peptide with a strong tendency to form β-structures, suggesting its association with amyloid fibrils. The full-length cDNA encoding NACP was isolated, and it encodes a 140-amino-acid protein. NACP is detected as a 19,000 kDa protein in brain homogenates and comigrates with bacterially synthesized NACP. NACP mRNA is predominantly expressed in the brain but is also present in low concentrations in other tissues, except the liver. The findings suggest that NAC may play a role in the formation of amyloid in AD by promoting the conformational change of soluble Aβ into insoluble amyloid.