Evidence map›Paper›PMID 26280122›Full record

ArticleNature medicine2015

APP intracellular domain-WAVE1 pathway reduces amyloid-β production.

Ilaria Ceglia, Christiane Reitz, Jodi Gresack, Jung-Hyuck Ahn, Victor Bustos, Marina Bleck, Xiaozhu Zhang, Grant Martin, Sanford M Simon, Angus C Nairn and 2 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.2field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 42 citations in OpenAlex.

  1. Biological psychiatry global open science · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

Ilaria CegliaLaboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York, USA.
Christiane ReitzThe Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.
Jodi GresackLaboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York, USA.
Jung-Hyuck AhnDepartment of Biochemistry, Ewha Womans University, Seoul, South Korea.
Victor BustosLaboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York, USA.
Marina BleckLaboratory of Cellular Biophysics, The Rockefeller University, New York, New York, USA.
Xiaozhu ZhangLaboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York, USA.
Grant MartinLaboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York, USA.
Sanford M SimonLaboratory of Cellular Biophysics, The Rockefeller University, New York, New York, USA.
Angus C NairnLaboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York, USA.
Paul GreengardLaboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York, USA.
Yong KimLaboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York, USA.
Rockefeller University · USColumbia University · USEwha Womans University · KRYale University · US

Funding

THE MECHANISMS OF y-SECRETASE REGULATIONP01AG009464 · NIA · ROCKEFELLER UNIVERSITY · PI KIM, YONG I · 1991 to 2011
$15.0M
Yale Alzheimer Disease Research CenterP50AG047270 · NIA · YALE UNIVERSITY · PI STRITTMATTER, STEPHEN M · 2015 to 2019
$8.3M
NIA NIH HHS AG009464NIA NIH HHS AG047270NIA NIH HHS P01 AG009464NIA NIH HHS P50 AG047270
6 · The paper itself

Abstract

An increase in amyloid-β (Aβ) production is a major pathogenic mechanism associated with Alzheimer's disease (AD), but little is known about possible homeostatic control of the amyloidogenic pathway. Here we report that the amyloid precursor protein (APP) intracellular domain (AICD) downregulates Wiskott-Aldrich syndrome protein (WASP)-family verprolin homologous protein 1 (WAVE1 or WASF1) as part of a negative feedback mechanism to limit Aβ production. The AICD binds to the Wasf1 promoter, negatively regulates its transcription and downregulates Wasf1 mRNA and protein expression in Neuro 2a (N2a) cells. WAVE1 interacts and colocalizes with APP in the Golgi apparatus. Experimentally reducing WAVE1 in N2a cells decreased the budding of APP-containing vesicles and reduced cell-surface APP, thereby reducing the production of Aβ. WAVE1 downregulation was observed in mouse models of AD. Reduction of Wasf1 gene expression dramatically reduced Aβ levels and restored memory deficits in a mouse model of AD. A decrease in amounts of WASF1 mRNA was also observed in human AD brains, suggesting clinical relevance of the negative feedback circuit involved in homeostatic regulation of Aβ production.

Indexed as

Amyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsBase SequenceCells, CulturedHumansMaleMiceMolecular Sequence DataProtein Structure, TertiarySignal TransductionWiskott-Aldrich Syndrome Protein FamilyAmyloid beta-PeptidesAmyloid beta-Protein PrecursorWiskott-Aldrich Syndrome Protein Family

Identifiers

PMID26280122
PMCPMC4560977
OpenAlexW1474396053

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.