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Peer-reviewedCC BY-NC-NDAlzheimer s & Dementia

Stable neuronal representations underlie cognitive resilience to Alzheimer's disease pathology

  • Keying Chen1,2
  • Emma Pineau3,1,2
  • Margaret M. Koletar1,2
  • Andrea Trevisiol1,2
  • Jie He4
  • Mary Hill5,1
  • Maged Goubran3,6,1,2
  • John G. Sled3,7,8,9
  • JoAnne McLaurin5,10,1
  • Bojana Stefanovic3,1,2
10 affiliations
  1. 1Hurvitz Brain Sciences Sunnybrook Health Sciences Centre Toronto Ontario Canada
  2. 2Physical Sciences Sunnybrook Research Institute Toronto Ontario Canada
  3. 3Department of Medical Biophysics University of Toronto Toronto Ontario Canada
  4. 4Faculty of Health Sciences McMaster University Hamilton Ontario Canada
  5. 5Biological Sciences Sunnybrook Research Institute Toronto Ontario Canada
  6. 6Harquail Centre for Neuromodulation Sunnybrook Health Sciences Centre Toronto Ontario Canada
  7. 7Department of Obstetrics & Gynecology University of Toronto Toronto Ontario Canada
  8. 8Mouse Imaging Centre The Hospital for Sick Children Toronto Ontario Canada
  9. 9Translational Medicine SickKids Research Institute Toronto Ontario Canada
  10. 10Department of Laboratory Medicine and Pathobiology Temerty Faculty of Medicine University of Toronto Toronto Ontario Canada
Open at sourceDOICite

Abstract

INTRODUCTION: While Alzheimer's disease (AD) typically elicits progressive cognitive decline, some individuals with significant AD pathology maintain cognition. Understanding the neuronal underpinnings of such cognitive resilience would propel the development of interventions for delaying dementia. METHODS: We used Barnes Maze testing to identify cognitively resilient 13-month-old TgF344-AD rats (established AD) and their non-transgenic littermates, followed by Neuropixels recording from 8500 neurons during repeated somatosensory stimulation, and culminating in post mortem tau and amyloid load quantifications. RESULTS: Cognitively resilient TgF344-AD rats recruited fewer neurons and displayed more stable neuronal representations during repeated stimulations in cortical excitatory and hippocampal inhibitory ensembles, with reduced excitatory spike burstiness and a distinct pattern of functional synaptic connectivity. These associations existed independently of amyloid levels. DISCUSSION: For the first time, our study revealed neuronal population-level hallmarks of maintained cognition that may serve as a novel neurophysiological biomarker of cognitive resilience and a target for stabilizing cognition.

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Cite

BibTeXRIS
BibTeX
@article{chen2026stable,
  title = {{Stable neuronal representations underlie cognitive resilience to Alzheimer's disease pathology}},
  author = {Keying Chen and Emma Pineau and Margaret M. Koletar and Andrea Trevisiol and Jie He and Mary Hill and Maged Goubran and John G. Sled and JoAnne McLaurin and Bojana Stefanovic},
  journal = {Alzheimer s \& Dementia},
  year = {2026},
  month = jun,
  doi = {10.1002/alz.71570},
  url = {https://doi.org/10.1002/alz.71570},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Stable neuronal representations underlie cognitive resilience to Alzheimer's disease pathology
AU  - Keying Chen
AU  - Emma Pineau
AU  - Margaret M. Koletar
AU  - Andrea Trevisiol
AU  - Jie He
AU  - Mary Hill
AU  - Maged Goubran
AU  - John G. Sled
AU  - JoAnne McLaurin
AU  - Bojana Stefanovic
PY  - 2026
DA  - 2026/06/01
JO  - Alzheimer s & Dementia
DO  - 10.1002/alz.71570
UR  - https://doi.org/10.1002/alz.71570
AB  - INTRODUCTION: While Alzheimer's disease (AD) typically elicits progressive cognitive decline, some individuals with significant AD pathology maintain cognition. Understanding the neuronal underpinnings of such cognitive resilience would propel the development of interventions for delaying dementia. METHODS: We used Barnes Maze testing to identify cognitively resilient 13-month-old TgF344-AD rats (established AD) and their non-transgenic littermates, followed by Neuropixels recording from 8500 neurons during repeated somatosensory stimulation, and culminating in post mortem tau and amyloid load quantifications. RESULTS: Cognitively resilient TgF344-AD rats recruited fewer neurons and displayed more stable neuronal representations during repeated stimulations in cortical excitatory and hippocampal inhibitory ensembles, with reduced excitatory spike burstiness and a distinct pattern of functional synaptic connectivity. These associations existed independently of amyloid levels. DISCUSSION: For the first time, our study revealed neuronal population-level hallmarks of maintained cognition that may serve as a novel neurophysiological biomarker of cognitive resilience and a target for stabilizing cognition.
SN  - 1552-5260
SN  - 1552-5279
ER  -