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Spatial pattern separation deficits in early Alzheimer’s disease are comparable in humans and animal models
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  • Published: 22 January 2026

Spatial pattern separation deficits in early Alzheimer’s disease are comparable in humans and animal models

  • Martina Laczó1 na1,
  • Kristyna Maleninska2,3 na1,
  • Natalie Khazaalova2,
  • Sarka Borovska1,
  • Martin Vyhnalek1,
  • Jakub Hort1,
  • Ales Stuchlik2 na1,
  • Jan Svoboda2 na1 &
  • …
  • Jan Laczó1 na1 

Scientific Reports , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Neurology
  • Neuroscience

Abstract

Spatial pattern separation (SPS) is a memory process that enables the discrimination of similar spatial locations. This process is vulnerable to pathophysiological changes in the early stages of Alzheimer’s disease (AD), but the translational potential of its testing remains unclear. This study aimed to evaluate the potential of SPS testing as a translational cognitive marker for identifying early AD and enabling direct comparisons of cognitive outcomes in animals and humans. We used a validated SPS task to examine biomarker-defined participants with amnestic mild cognitive impairment due to AD (AD aMCI; n = 56) and cognitively normal (CN) participants (n = 60). An animal version of this task, based on a modified Morris Water Maze task, was used to test six-month-old transgenic TgF344-AD rats (n = 38) and wild-type (WT) rats (n = 36). AD aMCI participants performed worse than CN participants, with performance declining as distance decreased. These results remained unchanged when adjusted for memory performance. TgF344-AD rats performed worse than WT rats in a probe trial with a 90° SPS design, but not in probe trials with an 180° SPS design or no SPS demands. The discriminatory power of the task was similar in the human and animal experiments. The findings demonstrate comparable SPS deficits in the early stages of AD in both humans and rodent models, which are not attributable to general memory impairment. SPS testing enables direct comparisons to be made between the cognitive performance of rats and humans, making it a promising approach for translational AD research.

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Data availability

All primary data from this study are detailed within the article. Any additional information and dataset required to reanalyse the data reported in this paper are available from the corresponding authors upon request.

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Acknowledgements

We would like to thank Ms M. Dokoupilova, Ms R. Svatkova, Ms V. Sedlakova, Ms N. Daniskova, Ms Z. Svacova, Dr H. Horakova, Dr V. Matuskova, Dr K. Veverova, Ms A. Katonova, Ms V. Jurasova, and Dr T. Nikolai for help with data collection; Dr J. Cerman, Dr I. Trubacik Mokrisova, and Dr J. Novakova Martinkova for help with participant recruitment; Mrs M. Radostova and Mrs V. Markova for technical support.

Funding

This study was supported by the National Institute for Neurological Research (Programme EXCELES, ID Project No. LX22NPO5107) – Funded by the European Union – Next Generation EU (ML, KM, NK, MV, JH, AS, JS, JL), Ministry of Health of the Czech Republic — conceptual development of research organization, University Hospital Motol, Prague, Czech Republic grant nr. 00064203 (ML, MV, JH, JL), the Institutional Support of Excellence 3 2. LF UK (Grant No. 6980382) (ML, JL, JH), Ministry of Health of the Czech Republic, grant nr. NW25-04-00337 (ML, JL), the Grant Agency of Charles University (Grant No. 40125) (ML), the Czech Science Foundation (GACR) registration number 22–33968S (ML, SB, MV, JH, JL) and 21–16667K (AS), Alzheimer’s Foundation (ML), and Martina Roeselová Memorial Fellowship (ML).

Author information

Author notes

  1. Martina Laczó, Kristyna Maleninska, Ales Stuchlik, Jan Svoboda and Jan Laczó contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Second Faculty of Medicine, Charles University, Motol and Homolka University Hospital, Prague, Czechia

    Martina Laczó, Sarka Borovska, Martin Vyhnalek, Jakub Hort & Jan Laczó

  2. Laboratory of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of Sciences, Prague, Czechia

    Kristyna Maleninska, Natalie Khazaalova, Ales Stuchlik & Jan Svoboda

  3. Center for Advanced Studies of Brain and Consciousness, National Institute of Mental Health, Klecany, Czechia

    Kristyna Maleninska

Authors
  1. Martina Laczó
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  2. Kristyna Maleninska
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  3. Natalie Khazaalova
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  4. Sarka Borovska
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  5. Martin Vyhnalek
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  6. Jakub Hort
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  8. Jan Svoboda
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  9. Jan Laczó
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Contributions

ML, KM, AS, JS and JL designed the study, interpreted the data, and drafted the manuscript. ML, KM, and JL analysed the data. NK and SB collected and interpreted the data, and critically reviewed the manuscript. JH and MV provided funding and critically reviewed the manuscript.

Corresponding authors

Correspondence to Jan Svoboda or Jan Laczó.

Ethics declarations

Competing interests

JH is a medical advisor at Neurona lab, Terrapino mobile app, consulted for Eisai, Eli Lilly, Biogen, Schwabe, and holds stock options in Alzheon. Other authors declare no competing interests.

Ethics approval and consent to participate

In the human study, all participants provided written informed consent, and the study was approved by the Ethics Committee of Motol University Hospital (consent number EK701/16). The study was performed in accordance with Alzheimer’s Association guidelines and the Declaration of Helsinki. In the animal study, the experimental and housing conditions were approved by the Resort Committee of Animal Welfare (51-2022-P) and complied with the European Community Council Directive (2010/63/EC).

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Laczó, M., Maleninska, K., Khazaalova, N. et al. Spatial pattern separation deficits in early Alzheimer’s disease are comparable in humans and animal models. Sci Rep (2026). https://doi.org/10.1038/s41598-026-36266-y

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  • Received: 11 October 2025

  • Accepted: 12 January 2026

  • Published: 22 January 2026

  • DOI: https://doi.org/10.1038/s41598-026-36266-y

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Keywords

  • Amyloid beta
  • Biomarkers
  • Memory
  • Morris water maze
  • Spatial learning
  • Translational test
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