Ramirez DM, Whitesell JD, Bhagwat N, Thomas TL, Ajay AD, Nawaby A, Delatour B, Bay S, Lafaye P, Knox JE, Harris JA, Meeks JP, Diamond MI. Endogenous pathology in tauopathy mice progresses via brain networks. 2023 May 24 10.1101/2023.05.23.541792 (version 1) bioRxiv.

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  1. This study explores the mechanisms of tau propagation through brain networks, using whole-brain staining methods with anti-p-tau nanobodies in 3D-imaged, P301S tau-mutated mice from 3 to 12 months old. The authors applied network propagation modeling to assess the relationship between structural connectivity and patterns of tau deposition across the whole brain. With their model, Denise Ramirez and colleagues report characteristic and non-random patterns of tau deposition over time, with a bias toward retrograde propagation.

    These results are concordant with previous functional and diffusion-weighted MRI studies suggesting that tau pathology follows connected regions in humans (Adams et al., 2019; Franzmeier et al., 2020; Jacobs et al., 2018). However, the limited spatial resolution of PET data constrains the mapping precision of human tau deposition in vivo. In addition, neuroimaging studies in humans are unable to determine the direction of propagation, i.e., anterograde versus retrograde.

    At a spatial resolution currently unthinkable at the human level, the results obtained through this innovative pipeline confirm that tau pathology preferentially propagates to structurally connected regions. This raises the question of the complementarity between diffusion-weighted and functional MRI techniques as predictors of tau propagation in humans.

    Future longitudinal studies comparing the two modalities would be useful to better approach their respective associations with tau spreading.

    References:

    Adams JN, Maass A, Harrison TM, Baker SL, Jagust WJ. Cortical tau deposition follows patterns of entorhinal functional connectivity in aging. Elife. 2019 Sep 2;8 PubMed.

    Franzmeier N, Neitzel J, Rubinski A, Smith R, Strandberg O, Ossenkoppele R, Hansson O, Ewers M, Alzheimer’s Disease Neuroimaging Initiative (ADNI). Functional brain architecture is associated with the rate of tau accumulation in Alzheimer's disease. Nat Commun. 2020 Jan 17;11(1):347. PubMed.

    Jacobs HI, Hedden T, Schultz AP, Sepulcre J, Perea RD, Amariglio RE, Papp KV, Rentz DM, Sperling RA, Johnson KA. Structural tract alterations predict downstream tau accumulation in amyloid-positive older individuals. Nat Neurosci. 2018 Mar;21(3):424-431. Epub 2018 Feb 5 PubMed.

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