Drieu A, Du S, Kipnis M, Bosch ME, Herz J, Lee C, Jiang H, Manis M, Ulrich JD, Kipnis J, Holtzman DM, Gratuze M. Parenchymal border macrophages regulate tau pathology and tau-mediated neurodegeneration. Life Sci Alliance. 2023 Nov;6(11) Print 2023 Nov PubMed.

Recommends

Please login to recommend the paper.

Comments

  1. The previous Nature paper by the authors (Drieu et al., 2022) has demonstrated that parenchymal border macrophages (PBM) contribute to cerebrospinal fluid (CSF) flow, possibly by trimming the extracellular matrix, and that depletion of PBM by CLO leads to abnormal CSF flow, causing an increase in Aβ accumulation. This interesting study employed a similar approach in the context of PS19 and showed that depletion of PBM using CLO exacerbates tau accumulation and neurodegeneration as well. Given that PBM likely have various functions beyond flow dynamics, further studies to determine whether the exacerbation of tau pathology is primarily due to abnormal CSF flow dynamics by PBM deletion may be warranted. In addition, the paper also highlighted that the number of MHCII positive PBM increased with age and in PS19 mice. It will also be interesting to investigate the roles of specific populations of PBMs on age- or tau-associated CSF flow dysfunction, if selective modulation of specific PBMs becomes feasible.

    References:

    Drieu A, Du S, Storck SE, Rustenhoven J, Papadopoulos Z, Dykstra T, Zhong F, Kim K, Blackburn S, Mamuladze T, Harari O, Karch CM, Bateman RJ, Perrin R, Farlow M, Chhatwal J, Dominantly Inherited Alzheimer Network, Hu S, Randolph GJ, Smirnov I, Kipnis J. Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid. Nature. 2022 Nov;611(7936):585-593. Epub 2022 Nov 9 PubMed.

    View all comments by Kaoru Yamada View all comments by Takeshi Iwatsubo

Make a Comment

To make a comment you must login or register.