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ALZHEIMER’S DISEASE

Imaging Alzheimer’s pathology stage by stage

Nature Aging volume 2, pages 465–467 (2022)Cite this article

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Tau neuropathology is a defining feature of Alzheimer’s disease. For decades, its progression throughout the cortex has been captured post mortem using Braak stages. A new study replicated Braak staging in living patients using positron emission tomography, showing associations with other biomarkers and clinical deficits.

Alzheimer’s disease (AD) neuropathology is characterized by the abnormal accumulation of two proteins: amyloid-β (Aβ) and hyperphosphorylated tau. The latter is strongly correlated with synaptic and neuronal dysfunction and with clinical deficits, over and above Aβ plaques1. Aβ plaques deposit in the cortex in a relatively diffuse manner, whereas tau-containing neurofibrillary tangles (NFT) follow a stereotypical progression that was described by Braak and Braak2 three decades ago. After observing thousands of brain samples, the authors described a six-stage system in which cortical NFTs first appear in medial temporal regions before extending to the inferolateral temporal cortices; later, NFTs reach associative neocortical areas, and eventually primary cortices2. This staging is a major component of the current criteria for the neuropathological diagnosis of AD3. But, with the recent development of tau-binding radiotracers for positron emission tomography (PET) in the 2010s4, can we now identify Braak stages in living patients? In this issue of Nature Aging, Therriault and colleagues5 applied an in vivo Braak staging algorithm to a large cross-sectional and longitudinal tau-PET dataset.

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Fig. 1: Tau-PET-based Braak staging, showing relationships with fluid biomarkers and cognitive impairment.

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Acknowledgements

The authors are supported by Race Against Dementia Alzheimer’s Research UK (ARUK-RADF2021A-010 to M.M.) and the National Institute on Aging (K99AG065501 to R.L.J.).

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Authors and Affiliations

  1. Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA

    Maura Malpetti & Renaud La Joie

  2. Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK

    Maura Malpetti

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  1. Maura Malpetti
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  2. Renaud La Joie
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Correspondence to Renaud La Joie.

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Malpetti, M., La Joie, R. Imaging Alzheimer’s pathology stage by stage. Nat Aging 2, 465–467 (2022). https://doi.org/10.1038/s43587-022-00236-6

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