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DEMENTIA

The phosphorylation cascade hypothesis of Alzheimer’s disease

Alzheimer’s disease (AD) is characterized by amyloid-β (Aβ)-induced phosphorylation of the axon-stabilizing tau protein, which causes neurodegeneration. Here, Morshed et al. show that deregulated phosphorylation in AD also affects other proteins and cell types in the brain, suggesting that the tau-centric view on Aβ toxicity should be revised.

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Fig. 1: Kinome map of all kinases with phosphopeptides that were significantly associated with tau or oligodendrocyte cluster centroids.

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Acknowledgements

Work in the authors’ laboratories is supported by the Swedish Research Council, the European Research Council, Swedish State Support for Clinical Research (ALFGBG), the Knut and Alice Wallenberg Foundation, and UK Dementia Research Institute at UCL. H.Z. is a Wallenberg Scholar.

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Correspondence to Gunnar Brinkmalm or Henrik Zetterberg.

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Competing interests

H.Z. has served at scientific advisory boards for Alector, Eisai, Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, Nervgen, AZTherapies and CogRx; has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure and Biogen; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside of submitted work). G.B. declares no competing interests.

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Brinkmalm, G., Zetterberg, H. The phosphorylation cascade hypothesis of Alzheimer’s disease. Nat Aging 1, 498–499 (2021). https://doi.org/10.1038/s43587-021-00077-9

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