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

• Published in: Nature communications Vol. 15; no. 1; pp. 4809 - 13
• Main Authors: Diez, Ibai, Ortiz-Terán, Laura, Ng, Thomas S. C, Albers, Mark W, Marshall, Gad, Orwig, William, Kim, Chan-mi, Bueichekú, Elisenda, Montal, Victor, Olofsson, Jonas, Vannini, Patrizia, El Fahkri, Georges, Sperling, Reisa, Johnson, Keith, Jacobs, Heidi I. L, Sepulcre, Jorge
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 06.06.2024; Nature Publishing Group UK; Nature Portfolio
• Subjects: Accumulation; Alzheimer's disease; Neurodegeneration; Neurodegenerative diseases; Odor; Odors; Older people; Olfactory discrimination; Olfactory pathways; Olfactory system; Perception; Positron emission; Tau protein; Temporal lobe; Transcriptomics
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-48462-3

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.The role of olfactory pathways in the development of neurodegeneration in Alzheimer’s disease is not well understood. Here, the authors show odor identification deficits are predictive of tau accumulation and progression in olfactory pathways, and that tau spreads from medial temporal lobe structures towards the olfactory system.