The amyloid precursor protein of Alzheimer disease is expressed as a 130 kDa polypeptide in various cultured cell types
- 5 December 1988
- journal article
- Published by Wiley in FEBS Letters
- Vol. 241 (1-2), 94-98
- https://doi.org/10.1016/0014-5793(88)81038-x
Abstract
The vascular and parenchymal amyloid deposits in Alzheimer disease (AD), normal aging and Down syndrome are mainly composed of a 4 kDa polypeptide (A4), which derives from a larger precursor protein (APP). There is evidence that APP is a transmembrane glycoprotein present in most tissues, but the characteristics of APP in intact cells are not yet known. In order to investigate this issue, we examined the immunoreactivity of fibroblasts of human and nonhuman cell lines with antisera raised to synthetic peptides corresponding to A4 and to two other domains of the APP. All three antisera recognized a 130 kDa polypeptide (APP‐130) in immunoblots from all cell lines. In fibroblasts, an additional polypeptide of 228 kDa (APP‐228) was recognized by the antiserum to A4. In immunoblots of two dimensional gels, APP‐130 showed a pI of 6.2, while APP‐228 failed to focus in the pH range of 4.7–7.0. Sequential extractions of cells with buffer and with Triton X‐100 indicate that APP‐130 is extractable with nonionic detergents at high ionic strength, whereas 228 kDa APP is a cystolic component. Immunofluorescence staining is consistent with an intracellular perinuclear and plasma membrane localization. It is concluded that APP‐130 and APP‐228 are two forms of the APP which result from extensive posttranslational modifications of a smaller original gene product. It is likely that APP undergoes similar posttranslational modifications in different cell types.Keywords
This publication has 17 references indexed in Scilit:
- Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activityNature, 1988
- Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's diseaseNature, 1988
- A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitorsNature, 1988
- Characterization and Chromosomal Localization of a cDNA Encoding Brain Amyloid of Alzheimer's DiseaseScience, 1987
- Amyloid β Protein Gene: cDNA, mRNA Distribution, and Genetic Linkage Near the Alzheimer LocusScience, 1987
- The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptorNature, 1987
- CHROMOSOME 21q21 SUBLOCALISATION OF GENE ENCODING BETA-AMYLOID PEPTIDE IN CEREBRAL VESSELS AND NEURITIC (SENILE) PLAQUES OF PEOPLE WITH ALZHEIMER DISEASE AND DOWN SYNDROMEThe Lancet, 1987
- Altered structural proteins in plaques and tangles: What do they tell us about the biology of Alzheimer's disease?Neurobiology of Aging, 1986
- Amyloid plaque core protein in Alzheimer disease and Down syndrome.Proceedings of the National Academy of Sciences, 1985
- Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid proteinBiochemical and Biophysical Research Communications, 1984