Evidence map›Paper›PMID 19710315›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009

The p75 neurotrophin receptor promotes amyloid-beta(1-42)-induced neuritic dystrophy in vitro and in vivo.

Juliet K Knowles, Jayakumar Rajadas, Thuy-Vi V Nguyen, Tao Yang, Melburne C LeMieux, Lilith Vander Griend, Chihiro Ishikawa, Stephen M Massa, Tony Wyss-Coray, Frank M Longo

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% 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

99 citing papers in PubMed, 1 synthesis or guideline pooled it, 189 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. A lifespan staging model of basal forebrain cholinergic vulnerability.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  6. Palmitoylation of death receptor p75Alzheimer's research & therapy · 2026
    Article
  7. Article
  8. Amelioration of Symptomatic Alzheimer's Disease after Selective Impairment of p75The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Small molecule modulation of p75Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Article
  15. Article
  16. Article
  17. Cholinergic Reinforcement Signaling Is Impaired by Amyloidosis Prior to Its Synaptic Loss.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023
    Article
  18. Article
  19. Article
  20. Article

39 more citing papers are in PubMed but not listed here.

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

10 authors at 4 institutions in 1 country.

Juliet K KnowlesDepartment of Neurology and Neurological Science, Stanford University, Stanford, California 94305, USA.
Jayakumar Rajadas
Thuy-Vi V Nguyen
Tao Yang
Melburne C LeMieux
Lilith Vander Griend
Chihiro Ishikawa
Stephen M Massa
Tony Wyss-Coray
Frank M Longo
Stanford University · USUniversity of North Carolina at Chapel Hill · USVA Palo Alto Health Care System · USUniversity of California, San Francisco · US

Funding

p75 -mediated protection from amyloid neurodegenerationF30NS051971 · NINDS · STANFORD UNIVERSITY · PI KNOWLES, JULIET KLASING · 2006 to 2008
$147k
NINDS NIH HHS F30 NS051971PHS HHS F30 NA051971
6 · The paper itself

Abstract

Oligomeric forms of amyloid-beta (Abeta) are thought to play a causal role in Alzheimer's disease (AD), and the p75 neurotrophin receptor (p75(NTR)) has been implicated in Abeta-induced neurodegeneration. To further define the functions of p75(NTR) in AD, we examined the interaction of oligomeric Abeta(1-42) with p75(NTR), and the effects of that interaction on neurite integrity in neuron cultures and in a chronic AD mouse model. Atomic force microscopy was used to ascertain the aggregated state of Abeta, and fluorescence resonance energy transfer analysis revealed that Abeta oligomers interact with the extracellular domain of p75(NTR). In vitro studies of Abeta-induced death in neuron cultures isolated from wild-type and p75(NTR-/-) mice, in which the p75(NTR) extracellular domain is deleted, showed reduced sensitivity of mutant cells to Abeta-induced cell death. Interestingly, Abeta-induced neuritic dystrophy and activation of c-Jun, a known mediator of Abeta-induced deleterious signaling, were completely prevented in p75(NTR-/-) neuron cultures. Thy1-hAPP(Lond/Swe) x p75(NTR-/-) mice exhibited significantly diminished hippocampal neuritic dystrophy and complete reversal of basal forebrain cholinergic neurite degeneration relative to those expressing wild-type p75(NTR). Abeta levels were not affected, suggesting that removal of p75(NTR) extracellular domain reduced the ability of excess Abeta to promote neuritic degeneration. These findings indicate that although p75(NTR) likely does not mediate all Abeta effects, it does play a significant role in enabling Abeta-induced neurodegeneration in vitro and in vivo, establishing p75(NTR) as an important therapeutic target for AD.

Indexed as

AcetylcholinesteraseAlzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnalysis of VarianceAnimalsCells, CulturedCell SurvivalDisease Models, AnimalEmbryo, MammalianEnzyme-Linked Immunosorbent AssayExonsFluorescence Resonance Energy TransferHippocampusHumansMiceAcetylcholinesteraseAmyloid beta-Peptidesamyloid beta-protein (1-42)Amyloid beta-Protein PrecursorPeptide FragmentsReceptor, Nerve Growth Factor

Identifiers

PMID19710315
PMCPMC2771439
OpenAlexW2090434536

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.