The Amyloid β Protein Precursor Mutations Linked to Familial Alzheimer's Disease Alter Processing in a Way That Fosters Amyloid Deposition

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Abstract

Younkin, S.G. The Amyloid β Protein Precursor Mutations Linked to Familial Alzheimer's Desease Alter Processing in a Way That Fosters Amyloid Deposition. Tohoku J. Exp. Med., 1994, 174 (3), 217-223 Normal processing of the amyloid β protein precursor (BAPP) results in secretion of a soluble 4 kD protein essentially identical to the amyloid β protein (Aβ) that forms insoluble fibrillar deposits in Alzheimer's disease (AD). Strong evidence that amyloid deposition plays a critical role in the development of AD has come from the identification of familial AD (FAD) kinderds in which the AD phenotype cose-gregates with mutations in the β APP gene that are located close to the NH2 or COOH end of the Aβ peptide. The location of these mutations immediately suggests that they may cause AD by altering β APP processing in a way that is amyloidogenic. In a previous study, we found that transfected cells expressing the NH2 side mutant secrete 6-fold more 4 kD Aβ than those expressing wild type β APP or COOH side mutants. We have now shown that the mutations on the COOH side of Aβ alter processing to increase secretion of the more amyloidogenic Aβ 1-42 form which constitutes only a small percentage of the total 4 kD Aβ produced. Thus our data show that all of the FAD-linked β APP mutations alter β APP processing in a way that increases the likelihood of amyloid formation. Alzheimer's disease; familial; amyloid; precursor; mutation.

Original languageEnglish (US)
Pages (from-to)217-223
Number of pages7
JournalTohoku Journal of Experimental Medicine
Volume174
Issue number3
DOIs
StatePublished - Jan 1 1994

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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