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

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 Fahkri, Reisa Sperling, Keith Johnson, Heidi I. L. Jacobs and Jorge Sepulcre ()
Additional contact information
Ibai Diez: Harvard Medical School
Laura Ortiz-Terán: Harvard Medical School
Thomas S. C. Ng: Harvard Medical School
Mark W. Albers: Harvard Medical School
Gad Marshall: Harvard Medical School
William Orwig: Harvard Medical School
Chan-mi Kim: Harvard Medical School
Elisenda Bueichekú: Harvard Medical School
Victor Montal: Harvard Medical School
Jonas Olofsson: Department of Psychology
Patrizia Vannini: Harvard Medical School
Georges El Fahkri: Harvard Medical School
Reisa Sperling: Harvard Medical School
Keith Johnson: Harvard Medical School
Heidi I. L. Jacobs: Harvard Medical School
Jorge Sepulcre: Harvard Medical School

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-48462-3

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