Evidence map›Paper›PMID 41916281›Full record

ArticleNeuron2026

Alzheimer's disease pathology degrades an NMDA receptor-dependent spontaneous activity pattern in cortico-hippocampal circuits.

Robert Ellingford, Samuel S Harris, Marten Kehring, Rikesh M Rajani, Francesca Kar Wey Lam, David Graykowski, Dorothea Bӧken, Lindsay A Welikovitch, Anita Khasnavis, Rhiannon Laban and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

22 authors.

Robert EllingfordUK Dementia Research Institute at University College London, London, UK. Electronic address: r.ellingford@ucl.ac.uk.
Samuel S HarrisUK Dementia Research Institute at University College London, London, UK.
Marten KehringUK Dementia Research Institute at University College London, London, UK.
Rikesh M RajaniUK Dementia Research Institute at University College London, London, UK; British Heart Foundation - UK Dementia Research Institute Centre for Vascular Dementia Research at The University of Edinburgh, Edinburgh, UK; Centre for Discovery Brain Sciences, The University of Edinburgh, Edinburgh, UK.
Francesca Kar Wey LamUK Dementia Research Institute at University College London, London, UK.
David GraykowskiUK Dementia Research Institute at University College London, London, UK.
Dorothea BӧkenYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK; UK Dementia Research Institute at University of Cambridge, Cambridge, UK.
Lindsay A WelikovitchDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Anita KhasnavisDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Rhiannon LabanUK Dementia Research Institute at University College London, London, UK.
Amanda HeslegraveUK Dementia Research Institute at University College London, London, UK; Department of Neurodegenerative Disease, University College London Queen Square Institute of Neurology, London, UK.
Umran YamanUK Dementia Research Institute at University College London, London, UK; Department of Neurodegenerative Disease, University College London Queen Square Institute of Neurology, London, UK.
Anastasie Mate de GerandoDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Suraya A BondUK Dementia Research Institute at University College London, London, UK.
Selina WrayDepartment of Neurodegenerative Disease, University College London Queen Square Institute of Neurology, London, UK.
Dervis A SalihUK Dementia Research Institute at University College London, London, UK.
David DupretMedical Research Council Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Raymond J DolanMax Planck UCL Centre for Computational Psychiatry and Ageing Research, London, UK.
David KlenermanYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK; UK Dementia Research Institute at University of Cambridge, Cambridge, UK.
Henrik ZetterbergUK Dementia Research Institute at University College London, London, UK.
Bradley T HymanDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Marc Aurel BuscheUK Dementia Research Institute at University College London, London, UK; Department of Neurodegenerative Diseases, University Hospital of Geriatric Medicine FELIX PLATTER and University of Basel, Basel, Switzerland; Department of Biomedicine, University of Basel, Basel, Switzerland; Department of Clinical Research, University of Basel, Basel, Switzerland. Electronic address: m.busche@ucl.ac.uk.

Funding

Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Christine S Ritchie · 2019 to 2026
$36.5M
Are multiple tau species toxic in Alzheimer's Disease?RF1AG059789 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HYMAN, BRADLEY T. · 2018 to 2018
$2.7M
NIA NIH HHS P30 AG062421NIA NIH HHS RF1 AG059789
6 · The paper itself

Abstract

Memory-based cognition relies on the integrity of cortico-hippocampal circuits, which are compromised in Alzheimer's disease (AD) as β-amyloid (Aβ) and tau accumulate. However, the mechanisms linking this pathology to circuit dysfunction remain unclear. In mouse models, using in vivo two-photon and Neuropixels recordings, we show that Aβ-tau pathology promotes both region- and layer-specific impairments, involving reduced burst firing in superficial cortical layers and CA1 and reduced mean firing of excitatory and inhibitory neurons in deep cortical layers and CA1. Exposure to Aβ primed the susceptibility of neuronal populations to tau-induced impairment. Combined Aβ-tau reduced synaptic NMDA receptor (NMDAR) density in both mouse and human tissue, while Aβ-tau co-reduction restored NMDARs and firing patterns and improved contextual memory. NMDAR antagonism in healthy mice phenocopied regional and laminar deficits. Our findings implicate synaptic NMDAR hypofunction as a reversible mechanism linking Aβ-tau synergy to cortico-hippocampal dysfunction in AD.

Indexed as

Alzheimer DiseaseCerebral CortexHippocampusReceptors, N-Methyl-D-AspartateAction PotentialsAmyloid beta-PeptidesAnimalsDisease Models, AnimalFemaleHumansMaleMiceMice, Inbred C57BLMice, TransgenicNeural PathwaysNeuronsAmyloid beta-PeptidesReceptors, N-Methyl-D-Aspartatetau ProteinsAlzheimer’s diseasecortical layerscortico-hippocampal circuitsmemory impairmentneurodegenerationNeuropixelsNMDARssynaptic dysfunctiontautwo-photon calcium imagingβ-amyloid

Identifiers

PMID41916281
PMCPMC13045655

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.