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Swollen axons impair neuronal circuits in Alzheimer’s disease

Abnormal protein aggregates are a hallmark of Alzheimer’s disease. It emerges that these plaques cause swellings in neuronal projections called axons that prevent proper circuit function.
By
  1. Inma Cobos

    1. Inma Cobos is in the Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.

  2. Jorge J. Palop

    1. Jorge J. Palop is at the Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, San Francisco, California 94158, USA.

Alzheimer’s disease is characterized by the abnormal accumulation of two misfolded proteins — amyloid-β, which forms structures called plaques outside cells, and tau inside cells. However, the effect of these aggregates on neuronal and network functions has been difficult to assess. The highly aggregated amyloid-β that makes up the core of plaques is surrounded by areas in which the synaptic connections between neurons have been lost1,2, and by neuronal projections called axons that have abnormal swellings, known as dystrophic neurites. Are these dystrophic neurites inert, or do they drive disease progression? Writing in Nature, Yuan et al.3 outline evidence suggesting that dystrophic neurites impair neuronal-circuit function, and provide mechanistic insights into this process.

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Nature 612, 218-220 (2022)

doi: https://doi.org/10.1038/d41586-022-03800-7

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Competing Interests

The authors declare no competing interests.

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