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Dissociation of tau pathology and neuronal hypometabolism within the ATN framework of Alzheimer’s disease

Author

Listed:
  • Michael Tran Duong

    (University of Pennsylvania
    University of Pennsylvania)

  • Sandhitsu R. Das

    (University of Pennsylvania
    University of Pennsylvania)

  • Xueying Lyu

    (University of Pennsylvania)

  • Long Xie

    (University of Pennsylvania)

  • Hayley Richardson

    (University of Pennsylvania)

  • Sharon X. Xie

    (University of Pennsylvania
    University of Pennsylvania)

  • Paul A. Yushkevich

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

  • David A. Wolk

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

  • Ilya M. Nasrallah

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

Abstract

Alzheimer’s disease (AD) is defined by amyloid (A) and tau (T) pathologies, with T better correlated to neurodegeneration (N). However, T and N have complex regional relationships in part related to non-AD factors that influence N. With machine learning, we assessed heterogeneity in 18F-flortaucipir vs. 18F-fluorodeoxyglucose positron emission tomography as markers of T and neuronal hypometabolism (NM) in 289 symptomatic patients from the Alzheimer’s Disease Neuroimaging Initiative. We identified six T/NM clusters with differing limbic and cortical patterns. The canonical group was defined as the T/NM pattern with lowest regression residuals. Groups resilient to T had less hypometabolism than expected relative to T and displayed better cognition than the canonical group. Groups susceptible to T had more hypometabolism than expected given T and exhibited worse cognitive decline, with imaging and clinical measures concordant with non-AD copathologies. Together, T/NM mismatch reveals distinct imaging signatures with pathobiological and prognostic implications for AD.

Suggested Citation

  • Michael Tran Duong & Sandhitsu R. Das & Xueying Lyu & Long Xie & Hayley Richardson & Sharon X. Xie & Paul A. Yushkevich & David A. Wolk & Ilya M. Nasrallah, 2022. "Dissociation of tau pathology and neuronal hypometabolism within the ATN framework of Alzheimer’s disease," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28941-1
    DOI: 10.1038/s41467-022-28941-1
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    1. Alexandra L Young & Razvan V Marinescu & Neil P Oxtoby & Martina Bocchetta & Keir Yong & Nicholas C Firth & David M Cash & David L Thomas & Katrina M Dick & Jorge Cardoso & John Swieten & Barbara Borr, 2018. "Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    2. Robert Thorndike, 1953. "Who belongs in the family?," Psychometrika, Springer;The Psychometric Society, vol. 18(4), pages 267-276, December.
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