Evidence map›Paper›PMID 27517085›Full record

ArticleeNeuro

APP Overexpression Causes Aβ-Independent Neuronal Death through Intrinsic Apoptosis Pathway.

Ning Cheng, Song Jiao, Ankita Gumaste, Li Bai, Leonardo Belluscio

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

Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

19 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
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

5 authors at 2 institutions in 1 country.

Ning ChengDevelopmental Neural Plasticity Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, Maryland 20892.
Song JiaoDevelopmental Neural Plasticity Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, Maryland 20892.
Ankita GumasteDevelopmental Neural Plasticity Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, Maryland 20892.
Li BaiDevelopmental Neural Plasticity Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, Maryland 20892.
Leonardo BelluscioDevelopmental Neural Plasticity Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, Maryland 20892.
National Institute of Neurological Disorders and Stroke · USNational Institutes of Health · US

Funding

Restoration of olfactory neural circuitry following disruption.ZIANS003116 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI BELLUSCIO, LEONARDO · 2010 to 2017
$6.5M
6 · The paper itself

Abstract

Accumulation of amyloid-β (Aβ) peptide in the brain is a central hallmark of Alzheimer's disease (AD) and is thought to be the cause of the observed neurodegeneration. Many animal models have been generated that overproduce Aβ yet do not exhibit clear neuronal loss, questioning this Aβ hypothesis. We previously developed an in vivo mouse model that expresses a humanized amyloid precursor protein (hAPP) in olfactory sensory neurons (OSNs) showing robust apoptosis and olfactory dysfunction by 3 weeks of age, which is consistent with early OSN loss and smell deficits, as observed in AD patients. Here we show, by deleting the β-site APP cleaving enzyme 1 (BACE1) in two distinct transgenic mouse models, that hAPP-induced apoptosis of OSNs is Aβ independent and remains cell autonomous. In addition, we reveal that the intrinsic apoptosis pathway is responsible for hAPP-induced OSN death, as marked by mitochondrial damage and caspase-9 activation. Given that hAPP expression causes OSN apoptosis despite the absence of BACE1, we propose that Aβ is not the sole cause of hAPP-induced neurodegeneration and that the early loss of olfactory function in AD may be based on a cell-autonomous mechanism, which could mark an early phase of AD, prior to Aβ accumulation. Thus, the olfactory system could serve as an important new platform to study the development of AD, providing unique insight for both early diagnosis and intervention.

Indexed as

Alzheimer DiseaseAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAnimalsApoptosisAspartic Acid EndopeptidasesBlotting, WesternBrainCaspase 9Disease Models, AnimalEnzyme-Linked Immunosorbent AssayHumansImmunohistochemistryMembrane Potential, MitochondrialMice, TransgenicMicroscopy, ElectronAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAPP protein, humanAspartic Acid EndopeptidasesBace1 protein, mouseCasp9 protein, mouseCaspase 9amyloid precursor proteinapoptosisneurodegenerationolfactory

Identifiers

PMID27517085
PMCPMC4967816
OpenAlexW2500547672

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.