Evidence map›Paper›PMID 40300603›Full record

ArticleCell2025

Alzheimer's disease patient-derived high-molecular-weight tau impairs bursting in hippocampal neurons.

Samuel S Harris, Robert Ellingford, Jana Hartmann, Debanjan Dasgupta, Marten Kehring, Rikesh M Rajani, David Graykowski, Noé Quittot, Dhanush Sivasankaran, Caitlin Commins and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing 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

25 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Amyloid β-dependent neuronal silencing through synaptic decoupling.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  19. Article
  20. Small-diffusible aggregates, plaques, tangles, and dynamic equilibria: Untangling Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    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

19 authors.

Samuel S HarrisUK Dementia Research Institute at University College London, London, UK. Electronic address: samuel.harris@ucl.ac.uk.
Robert EllingfordUK Dementia Research Institute at University College London, London, UK.
Jana HartmannUK Dementia Research Institute at University College London, London, UK.
Debanjan DasguptaUK 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.
David GraykowskiUK Dementia Research Institute at University College London, London, UK.
Noé QuittotDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Dhanush SivasankaranDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Caitlin ComminsDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Zhanyun FanDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Suraya A BondUK Dementia Research Institute at University College London, London, UK.
Fred WolfGöttingen Campus Institute for Dynamics of Biological Networks, Göttingen, Germany.
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.
Arthur KonnerthInstitute of Neuroscience, Technical University of Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
Andreas NeefGöttingen Campus Institute for Dynamics of Biological Networks, Göttingen, Germany.
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. Electronic address: m.busche@ucl.ac.uk.

Funding

Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Christine S Ritchie · 2019 to 2026
$36.5M
LRP1-tau interactions and Alzheimer DiseaseRF1AG073236 · NIA · UNIVERSITY OF MARYLAND BALTIMORE · PI HYMAN, BRADLEY T., STRICKLAND, DUDLEY K. · 2021 to 2021
$2.4M
Upgrading the CVID Biosensor Core Facility with a Biacore 8K instrumentS10OD030379 · OD · UNIVERSITY OF MARYLAND BALTIMORE · PI STRICKLAND, DUDLEY K. · 2021 to 2021
$439k
NIA NIH HHS P30 AG062421NIA NIH HHS RF1 AG073236NIH HHS S10 OD030379
6 · The paper itself

Abstract

Tau accumulation is closely related to cognitive symptoms in Alzheimer's disease (AD). However, the cellular drivers of tau-dependent decline of memory-based cognition remain elusive. Here, we employed in vivo Neuropixels and patch-clamp recordings in mouse models and demonstrate that tau, independent of β-amyloid, selectively debilitates complex-spike burst firing of CA1 hippocampal neurons, a fundamental cellular mechanism underpinning learning and memory. Impaired bursting was associated with altered hippocampal network activities that are coupled to burst firing patterns (i.e., theta rhythms and high-frequency ripples) and was concurrent with reduced neuronal expression of CaV2.3 calcium channels, which are essential for burst firing in vivo. We subsequently identify soluble high molecular weight (HMW) tau, isolated from human AD brain, as the tau species responsible for suppression of burst firing. These data provide a cellular mechanism for tau-dependent cognitive decline in AD and implicate a rare species of intracellular HMW tau as a therapeutic target.

Indexed as

Alzheimer DiseaseHippocampusNeuronstau ProteinsAction PotentialsAgedAnimalsCA1 Region, HippocampalDisease Models, AnimalFemaleHumansMaleMiceMice, Inbred C57BLMice, TransgenicMolecular Weighttau ProteinsAlzheimer’s diseaseCaV2.3 (R-type) channelsextracellular electrophysiologyhigh molecular weight tauhippocampus CA1humanmouse modelsneuronal burstingpatch-clamp electrophysiology

Identifiers

PMID40300603
PMCPMC12255526

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.