Evidence map›Paper›PMID 40302031›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Inhibition of hippocampal mossy fiber plasticity and episodic memory by human Aβ oligomers is prevented by enhancing cAMP signaling in Alzheimer's mice.

Shan-Xue Jin, Jean-Pierre Bellier, Adrienne Wells, Paula Montero LIopis, Praju Vikas Anekal, Jason S Tresback, Barbara J Caldarone, Lei Liu, Shaomin Li, Ulf Dettmer and 2 more

Abstract read
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Reduction in hippocampal cholinergic neurostimulating peptide enhances memory impairment in AppAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  4. Boosting Neurogenesis as a Strategy in Treating Alzheimer's Disease.International journal of molecular sciences · 2025
    Review
  5. 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

12 authors.

Shan-Xue JinAnn Romney Center for Neurologic Diseases, Department of Neurology, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.
Jean-Pierre BellierAnn Romney Center for Neurologic Diseases, Department of Neurology, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.
Adrienne WellsMicRoN Core, Harvard Medical School, Boston, Massachusetts, USA.
Paula Montero LIopisMicRoN Core, Harvard Medical School, Boston, Massachusetts, USA.
Praju Vikas AnekalMicRoN Core, Harvard Medical School, Boston, Massachusetts, USA.
Jason S TresbackCenter for Nanoscale Systems, Harvard University, Cambridge, Massachusetts, USA.
Barbara J CaldaroneMouse Behavior Core, Harvard Medical School, Boston, Massachusetts, USA.
Lei LiuAnn Romney Center for Neurologic Diseases, Department of Neurology, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.
Shaomin LiAnn Romney Center for Neurologic Diseases, Department of Neurology, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.
Ulf DettmerAnn Romney Center for Neurologic Diseases, Department of Neurology, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.
Nagendran RamalingamAnn Romney Center for Neurologic Diseases, Department of Neurology, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.
Dennis J SelkoeAnn Romney Center for Neurologic Diseases, Department of Neurology, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.

Funding

TRANSGENICS AND PRESENILIN FUNCTIONP01AG015379 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI BEREZOVSKA, OKSANA, SELKOE, DENNIS J · 1998 to 2023
$51.3M
NIH Blueprint for Neuroscience Research P01AG015379NIH Blueprint for Neuroscience Research RO1AG006173The Davis Alzheimer's Prevention Program
6 · The paper itself

Abstract

introductionEarly episodic memory impairment in Alzheimer's disease (AD) is linked to synaptic dysfunction from amyloid β-protein oligomers (oAβ), particularly affecting the dentate gyrus mossy fiber-CA3 pathway. The APP

methodsWe administered the β-adrenergic receptor agonist isoproterenol (ISO) in vivo and phosphodiesterase type 4 inhibitor GSK356278 in vitro to assess their impact on mf-LTP and contextual fear memory. Fluorescence lifetime imaging (FLIM)-Förster resonance energy transfer (FRET) microscopy was used to visualize impaired and rescued cyclic adenosine monophosphate (cAMP) signaling in dentate gyrus neurons.

resultsISO prevented mf-LTP impairment at 3-4 mo and improved memory by 7 mo. GSK356278 inhibited mf-LTP deficits in a dose-dependent manner. ISO also reduced hyperphosphorylation of synapsin I and microgliosis. DISCUSSION: These findings suggest that β-AR activation and phosphodiesterase 4 (PDE4) inhibition mitigate oAβ-induced memory deficits, supporting enhanced cAMP signaling as a therapeutic target for early AD. HIGHLIGHTS: Early episodic memory deficits in AD linked to oAβ-induced synaptic dysfunction. Isoproterenol and GSK356278 improve mossy fiber-LTP and fear memory deficits. FLIM-FRET shows treatments restore cAMP signaling in dentate gyrus neurons. Isoproterenol reduces synapsin I hyperphosphorylation and microgliosis. Enhancing cAMP signaling may help mitigate early memory deficits in AD.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesCyclic AMPMemory, EpisodicMossy Fibers, HippocampalNeuronal PlasticityAdrenergic beta-AgonistsAnimalsDisease Models, AnimalHumansIsoproterenolLong-Term PotentiationMaleMiceMice, TransgenicPhosphodiesterase 4 InhibitorsAdrenergic beta-AgonistsAmyloid beta-PeptidesCyclic AMPIsoproterenolPhosphodiesterase 4 InhibitorsAlzheimer's diseaseAPPNL‐G‐F knock‐in miceAβ oligomerscAMPepisodic memoryFLIM‐FRETlong‐term potentiationmicrogliosismossy fiber‐CA3 pathwayβ‐adrenergic signaling

Identifiers

PMID40302031
PMCPMC12040739

What OpenQuestion holds

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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.