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Tau propagation in the brain olfactory circuits is associated with smell perception changes in aging

Author

Listed:
  • Ibai Diez

    (Harvard Medical School
    Harvard Medical School)

  • Laura Ortiz-Terán

    (Harvard Medical School
    UMASS Chan Medical School)

  • Thomas S. C. Ng

    (Harvard Medical School
    Harvard Medical School)

  • Mark W. Albers

    (Harvard Medical School)

  • Gad Marshall

    (Harvard Medical School)

  • William Orwig

    (Harvard Medical School
    Department of Psychology)

  • Chan-mi Kim

    (Harvard Medical School)

  • Elisenda Bueichekú

    (Harvard Medical School)

  • Victor Montal

    (Harvard Medical School
    Barcelona Supercomputing Center)

  • Jonas Olofsson

    (Department of Psychology)

  • Patrizia Vannini

    (Harvard Medical School
    Harvard Medical School)

  • Georges El Fahkri

    (Harvard Medical School)

  • Reisa Sperling

    (Harvard Medical School
    Harvard Medical School
    Harvard Medical School)

  • Keith Johnson

    (Harvard Medical School)

  • Heidi I. L. Jacobs

    (Harvard Medical School)

  • Jorge Sepulcre

    (Harvard Medical School
    Harvard Medical School)

Abstract

The direct access of olfactory afferents to memory-related cortical systems has inspired theories about the role of the olfactory pathways in the development of cortical neurodegeneration in Alzheimer’s disease (AD). In this study, we used baseline olfactory identification measures with longitudinal flortaucipir and PiB PET, diffusion MRI of 89 cognitively normal older adults (73.82 ± 8.44 years; 56% females), and a transcriptomic data atlas to investigate the spatiotemporal spreading and genetic vulnerabilities of AD-related pathology aggregates in the olfactory system. We find that odor identification deficits are predominantly associated with tau accumulation in key areas of the olfactory pathway, with a particularly strong predictive power for longitudinal tau progression. We observe that tau spreads from the medial temporal lobe structures toward the olfactory system, not the reverse. Moreover, we observed a genetic background of odor perception-related genes that might confer vulnerability to tau accumulation along the olfactory system.

Suggested Citation

  • Ibai Diez & Laura Ortiz-Terán & Thomas S. C. Ng & Mark W. Albers & Gad Marshall & William Orwig & Chan-mi Kim & Elisenda Bueichekú & Victor Montal & Jonas Olofsson & Patrizia Vannini & Georges El Fahk, 2024. "Tau propagation in the brain olfactory circuits is associated with smell perception changes in aging," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48462-3
    DOI: 10.1038/s41467-024-48462-3
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    References listed on IDEAS

    as
    1. Liam Drew, 2022. "Olfactory receptors are not unique to the nose," Nature, Nature, vol. 606(7915), pages 14-17, June.
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