Cited by 195Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Soluble amyloid precursor protein-α modulates β-secretase activity and amyloid-β generation

Open access
Obregon, Demian, Hou, Huayan, Deng, Juan, Giunta, Brian, Tian, Jun, Darlington, Donna, Shahaduzzaman, Md, Zhu, Yuyuan +3 more·2012·Nature Communications

Abstract

In sporadic age-related forms of Alzheimer's disease (AD), it is unclear why amyloid-β (Aβ) peptides accumulate. Here we show that soluble amyloid precursor protein-α (sAPP-α) decreases Aβ generation by directly associating with β-site APP-converting enzyme (BACE)1, thereby modulating APP processing. Whereas specifically targeting sAPP-α using antibodies enhances Aβ production; in transgenic mice with AD-like pathology, sAPP-α overexpression decreases β-amyloid plaques and soluble Aβ. In support, immunoneutralization of sAPP-α increases APP amyloidogenic processing in these mice. Given our current findings, and because a number of risk factors for sporadic AD serve to lower levels of sAPP-α in brains of AD patients, inadequate sAPP-α levels may be sufficient to polarize APP processing towards the amyloidogenic, Aβ-producing route. Therefore, restoration of sAPP-α or enhancement of its association with BACE may be viable strategies to ameliorate imbalances in APP processing that can lead to AD pathogenesis.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/ncomms1781

Cites

59 of 59 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

1 retracted

Flagged first, then by citations

1 of the 60 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. [42]Milne JC Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes Nature 450 712 716 2007 18046409 PMC2753457

Cited by

Sorted by citations

Authors
Obregon, D., Hou, H., Deng, J., Giunta, B., Tian, J., Darlington, D., Shahaduzzaman, M., Zhu, Y., Mori, T., Mattson, M. P., & Tan, J.
Affiliations
  • University of South Florida (US)
  • Social Insurance Saitama Chuo Hospital (JP)
  • National Institute on Aging (US)
Corresponding author
Tan, Jun
Venue
Nature Communications
Published
2012-04-10
Volume
3
Issue
1
Pages
777-777
ISSN
2041-1723 (ISSN-L)
OpenAlex
W2065184914
Cited by
192
References
60
Citations by year
2026: 14 · 2025: 13 · 2024: 14 · 2023: 16 · 2022: 11 · 2021: 18 · 2020: 14 · 2019: 12 · 2018: 18 · 2017: 12 · 2016: 15 · 2015: 12 · 2014: 10 · 2013: 10 · 2012: 2
FWCI
7.29
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • U.S. Department of Veterans Affairs
  • Office of Research and Development
  • National Institutes of Health
  • Japan Society for the Promotion of Science (22500320)
  • National Institute on Aging (R42AG031586, R01AG032432)
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
sAPPα, BACE1, beta-secretase, amyloid-beta production, APP processing, Alzheimer's disease, amyloid plaques, neurotrophic factors, sporadic Alzheimer's disease, transgenic mouse model, immunoneutralization
MeSH terms
Alzheimer Disease, Animals, Cell Line, Humans, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Transgenic, Protein Processing, Post-Translational, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, Amyloid beta-Protein Precursor, Amino Acid Motifs, Mice, Amyloid Precursor Protein Secretases

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