Staging Alzheimer’s disease on the basis of the disease’s biological underpinnings might help with stratification and prognostication, both in the clinical setting and in clinical trials. We propose a staging model based on only five biomarkers, which are related to amyloid-β and tau pathologies in different ways and can be measured with a single sample of cerebrospinal fluid.
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References
Vogel, J. W. et al. Four distinct trajectories of tau deposition identified in Alzheimer’s disease. Nat. Med. 27, 871–881 (2021). In this paper, we described four different trajectories for tau deposition, which are useful for staging patients with AD.
Barthélemy, N. et al. A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease. Nat. Med. 26, 398–407 (2020). This paper reports that changes in the levels of site-specific tau phosphorylation occur at different stages of AD progression.
Salvadó, G. et al. Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads. EMBO Mol. Med. 15, e2463 (2023). This paper reports the distinct correlation of tau biomarkers hyperphosphorylated at different epitopes with levels of Aβ plaques and tau tangles.
Wesseling, H. et al. Tau PTM profiles identify patient heterogeneity and stages of Alzheimer’s disease. Cell 183, 1699–1713 (2020). This paper linked different post-translational tau modifications with different disease stages.
Young, A. L. et al. Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference. Nat. Commun. 9, 4273 (2018). This paper reports the derivation of SuStaIn, the data-driven model we used to create our staging model.
Horie, K. et al. CSF MTBR-tau243 is a specific biomarker of tau tangle pathology in Alzheimer’s disease. Nat. Med. 8, 1954–1963 (2023). This paper validates the CSF biomarker MTBR-tau243 in two independent cohorts and shows its tight correlation with tau tangle pathology.
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This is a summary of: Salvadó, G. et al. Disease staging of Alzheimer’s disease using a CSF-based biomarker model. Nat. Aging https://doi.org/10.1038/s43587-024-00599-y (2024).
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Five biomarkers from one cerebrospinal fluid sample to stage Alzheimer’s disease. Nat Aging (2024). https://doi.org/10.1038/s43587-024-00618-y
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DOI: https://doi.org/10.1038/s43587-024-00618-y
