Evidence map›Paper›PMID 37909036›Full record

ArticleNeuron2024

Localized APP expression results in progressive network dysfunction by disorganizing spike timing.

Silvia Viana da Silva, Matthias G Haberl, Kshitij Gaur, Rina Patel, Gautam Narayan, Max Ledakis, Maylin L Fu, Miguel de Castro Vieira, Edward H Koo, Jill K Leutgeb and 1 more

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

Article in Neuron, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

7 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. NPAS4 refines spatial and temporal firing in CA1 pyramidal neurons.bioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. From local APP expression to network dysfunction.Nature reviews. Neuroscience · 2024
    Article
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

11 authors at 3 institutions in 2 countries.

Silvia Viana da SilvaNeurobiology Department, School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA; NeuroCure Excellence Cluster and German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
Matthias G HaberlCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Neuroscience Research Center, Charitéplatz 1, 10117 Berlin, Germany.
Kshitij GaurNeurobiology Department, School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
Rina PatelNeurobiology Department, School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
Gautam NarayanNeurobiology Department, School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
Max LedakisNeurobiology Department, School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
Maylin L FuNeurobiology Department, School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
Miguel de Castro VieiraCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Neuroscience Research Center, Charitéplatz 1, 10117 Berlin, Germany.
Edward H KooDepartment of Neurosciences, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
Jill K LeutgebNeurobiology Department, School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA. Electronic address: jleutgeb@ucsd.edu.
Stefan LeutgebNeurobiology Department, School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA; Kavli Institute for Brain and Mind, University of California, San Diego, La Jolla, CA, USA. Electronic address: sleutgeb@ucsd.edu.
University of California San Diego · USHumboldt-Universität zu Berlin · DEGerman Center for Neurodegenerative Diseases · DE

Funding

Memory processing after neuron loss in the entorhinal cortex and hippocampusR01NS086947 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LEUTGEB, STEFAN · 2014 to 2024
$3.9M
Dependence of memory on precisely coordinated oscillationsR01NS102915 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Stefan Leutgeb · 2017 to 2026
$3.1M
Mechanisms of abeta induced dysfunction in hippocampal neuronal circuitryR01NS084324 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KOO, EDWARD H., LEUTGEB, STEFAN · 2014 to 2018
$2.7M
Connectivity and function of microcircuits in the superficial layers of the entorhinal cortexR01NS097772 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LEUTGEB, STEFAN, LIM, BYUNGKOOK · 2017 to 2021
$2.0M
Hippocampal network mechanisms for memory-guided behaviorR01MH119179 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LEUTGEB, JILL K · 2019 to 2023
$1.8M
NIMH NIH HHS R01 MH119179NINDS NIH HHS R01 NS084324NINDS NIH HHS R01 NS086947NINDS NIH HHS R01 NS097772NINDS NIH HHS R01 NS102915
6 · The paper itself

Abstract

Progressive cognitive decline in Alzheimer's disease could either be caused by a spreading molecular pathology or by an initially focal pathology that causes aberrant neuronal activity in a larger network. To distinguish between these possibilities, we generated a mouse model with expression of mutant human amyloid precursor protein (APP) in only hippocampal CA3 cells. We found that performance in a hippocampus-dependent memory task was impaired in young adult and aged mutant mice. In both age groups, we then recorded from the CA1 region, which receives inputs from APP-expressing CA3 cells. We observed that theta oscillation frequency in CA1 was reduced along with disrupted relative timing of principal cells. Highly localized pathology limited to the presynaptic CA3 cells is thus sufficient to cause aberrant firing patterns in postsynaptic neuronal networks, which indicates that disease progression is not only from spreading pathology but also mediated by progressively advancing physiological dysfunction.

Indexed as

Alzheimer DiseaseAmyloid beta-Protein PrecursorAgedAnimalsHippocampusHumansMiceMice, TransgenicNeuronsSynapsesAmyloid beta-Protein PrecursorAlzheimer’s diseaseamyloid precursor proteinhippocampusphase precessionspike timingtheta oscillations

Identifiers

PMID37909036
PMCPMC10877582
OpenAlexW4388024586

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.