Cited by 1,921Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Amyloid β-peptide is produced by cultured cells during normal metabolism

Haass, Christian, Schlossmacher, Michael G., Hung, Albert Y., Vigo-Pelfrey, Carmen, Mellon, Angela, Ostaszewski, Beth L., Lieberburg, Ivan, Koo, Edward H. +3 more·1992·Nature

Abstract

Alzheimer's disease is characterized by the extracellular deposition in the brain and its blood vessels of insoluble aggregates of the amyloid beta-peptide (A beta), a fragment, of about 40 amino acids in length, of the integral membrane protein beta-amyloid precursor protein (beta-APP). The mechanism of extracellular accumulation of A beta in brain is unknown and no simple in vitro or in vivo model systems that produce extracellular A beta have been described. We report here the unexpected identification of the 4K (M(r) 4,000) A beta and a truncated form of A beta (approximately 3K) in media from cultures of primary cells and untransfected and beta-APP-transfected cell lines grown under normal conditions. These peptides were immunoprecipitated readily from culture medium by A beta-specific antibodies and their identities confirmed by sequencing. The concept that pathological processes are responsible for the production of A beta must not be reassessed in light of the observation that A beta is produced in soluble form in vitro and in vivo during normal cellular metabolism. Further, these findings provide the basis for using simple cell culture systems to identify drugs that block the formation or release of A beta, the primary protein constituent of the senile plaques of Alzheimer's disease.

Integrity signals

Registry

Crossref · 10.1038/359322a0

Cites

17 of 17 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Normal processing of β-APP secretes 4-kDa Aβ that is readily detected in human cerebrospinal fluid and in medium conditioned by cultured cells.

    “Recently, we and others have shown that normal processing of the large amyloid f3 protein precursor ({3-APP) secretes 4-kDa A(3 that is readily detected in human cerebrospinal fluid and in medium conditioned by cultured cells (3)(4)(5)(6).”

    From Amyloid β Protein (Aβ) in Alzheimeri's Disease Brain (1995) · cites this paper as [4]

  • High BACE1 enzymatic activity is found in human AD brain extracts.

    “High BACE1 enzymatic activity was found in human AD brain extracts, which is consistent with the finding that neurons produce the highest levels of Aβ (3,45).”

    From The β-Secretase BACE1 in Alzheimer’s Disease (2021) · cites this paper as [45]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Haass, C., Schlossmacher, M. G., Hung, A. Y., Vigo-Pelfrey, C., Mellon, A., Ostaszewski, B. L., Lieberburg, I., Koo, E. H., Schenk, D., Teplow, D. B., & Selkoe, D. J.
Affiliations
  • Harvard University (US)
  • Brigham and Women's Hospital (US)
Venue
Nature
Published
1992-09
Volume
359
Issue
6393
Pages
322-325
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W1979543098
Cited by
1,921
References
17
Citations by year
2026: 12 · 2025: 14 · 2024: 22 · 2023: 15 · 2022: 19 · 2021: 28 · 2020: 31 · 2019: 25 · 2018: 29 · 2017: 35 · 2016: 43 · 2015: 46 · 2014: 51 · 2013: 43 · 2012: 67
FWCI
80.93
Type
journal article
Language
en
Open access
closed
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
amyloid-beta, Alzheimer's disease, amyloid precursor protein, amyloid plaques, cell culture model, drug screening
MeSH terms
Antibodies, Epitopes, Cell Line, DNA, Humans, Kidney, Methionine, Molecular Weight, Recombinant Proteins, Transfection, Amyloid beta-Peptides, Amyloid beta-Protein Precursor

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review