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NEURODEGENERATION

Is presymptomatic ALS perivascular?

Nature Medicine volume 27, pages 585–586 (2021)Cite this article

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Increased activity in perivascular fibroblasts could precede motor-neuron degeneration and be a predictor of shorter survival in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease classically defined by progressive loss of motor neurons. Work in recent decades has revealed several genes encoding proteins responsible for ALS, although the majority (80–90%) of ALS cases have no known genetic cause. In addition, the underlying pathogenesis of ALS remains poorly understood, which has limited treatment options, and the currently available medications are only minimally effective. While loss of motor neurons drives the clinical manifestations of ALS, mounting evidence shows other cell types are crucial in driving the degeneration of these neurons1. In this issue, Månberg et al. describe a potential role for perivascular fibroblasts (PVFs) in the pathogenesis of ALS; they use human postmortem tissue and transgenic models of ALS to define changes in genetic expression patterns associated with end-stage ALS and the progression of ALS2. Strikingly, the authors find that markers of increased PVF activity may be an early event in the pathogenesis of ALS and may be predictive of shorter survival.

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Fig. 1: PVFs may contribute to early ALS pathogenesis.

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Authors and Affiliations

  1. Department of Neurology, Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO, USA

    Collin J. Kreple, Kathleen M. Schoch & Timothy M. Miller

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  1. Collin J. Kreple
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  2. Kathleen M. Schoch
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  3. Timothy M. Miller
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Correspondence to Timothy M. Miller.

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Competing interests

T.M.M. reports serving on the advisory board of Biogen, consulting for and a license agreement with Ionis Pharmaceuticals, consulting for Disarm Therapeutics and Cytokinetics, and a licensing agreement with C2N.

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Kreple, C.J., Schoch, K.M. & Miller, T.M. Is presymptomatic ALS perivascular?. Nat Med 27, 585–586 (2021). https://doi.org/10.1038/s41591-021-01311-y

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