Beta-amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues

Dennis J Selkoe; Marcia Berman Podlisny; Catharine L Joachim; Elizabeth A Vickers; Gloria Lee; Lawrence C Fritz; Tilman Oltersdorf

doi:10.1073/pnas.85.19.7341

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Beta-amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues

Journal article

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Beta-amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues

Dennis J Selkoe, Marcia Berman Podlisny, Catharine L Joachim, Elizabeth A Vickers, Gloria Lee, Lawrence C Fritz and Tilman Oltersdorf

Proceedings of the National Academy of Sciences - PNAS, Vol.85(19), pp.7341-7345

10/1988

DOI: 10.1073/pnas.85.19.7341

PMCID: PMC282182

PMID: 3140239

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Abstract

Progressive cerebral deposition of extracellular filaments composed of the beta-amyloid protein (beta AP) is a constant feature of Alzheimer disease (AD). Since the gene on chromosome 21 encoding the beta AP precursor (beta APP) is not known to be altered in AD, transcriptional or posttranslational changes may underlie accelerated beta AP deposition. Using two antibodies to the predicted carboxyl terminus of beta APP, we have identified the native beta APP in brain and nonneural human tissues as a 110- to 135-kDa protein complex that is insoluble in buffer and found in various membrane-rich subcellular fractions. These proteins are relatively uniformly distributed in adult brain, abundant in fetal brain, and detected in nonneural tissues that contain beta APP mRNA. Similarly sized proteins occur in rat, cow, and monkey brain and in cultured human HL-60 and HeLa cells; the precise patterns in the 110- to 135-kDa range are heterogeneous among various tissues and cell lines. Confirmation that the immunodetected tissue proteins are forms of beta APP was obtained when mammalian cells transfected with a full-length beta APP cDNA showed selectively augmented expression of 110- to 135-kDa proteins and specific immunocytochemical staining. Unexpectedly, the antibodies to the carboxyl terminus of beta APP labeled amyloid-containing senile plaques in AD brain. We conclude that the highly conserved beta APP molecule occurs in mammalian tissues as a heterogeneous group of membrane-associated proteins of approximately 120 kDa. Detection of the nonamyloidogenic carboxyl terminus within plaques suggests that proteolytic processing of the beta APP into insoluble filaments occurs locally in cortical regions that develop beta-amyloid deposits with age.

Antibodies

Transfection

Amyloid - genetics

Molecular Weight

Protein Precursors - genetics

Protein Precursors - analysis

Humans

RNA, Messenger - analysis

Amyloid - analysis

Membrane Proteins - analysis

DNA - analysis

Alzheimer Disease - metabolism

Amyloid beta-Peptides

Brain - pathology

Brain Chemistry

Chromosomes, Human, Pair 21

Amyloid beta-Protein Precursor

Details

Title: Subtitle: Beta-amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues
Creators: Dennis J Selkoe - Harvard Medical School
Marcia Berman Podlisny - Harvard Medical School
Catharine L Joachim - Harvard Medical School
Elizabeth A Vickers - Harvard Medical School
Gloria Lee - Harvard Medical School
Lawrence C Fritz - Harvard Medical School
Tilman Oltersdorf - Harvard Medical School
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.85(19), pp.7341-7345
DOI: 10.1073/pnas.85.19.7341
PMID: 3140239
PMCID: PMC282182
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences; United States
Grant note: AG 06173 / NIA NIH HHS AG 07241 / NIA NIH HHS
Language: English
Date published: 10/1988
Academic Unit: Iowa Neuroscience Institute; Immunology; Internal Medicine
Record Identifier: 9984065398402771

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