Alzheimer’s Research & Therapy (Feb 2023)

Associations between different tau-PET patterns and longitudinal atrophy in the Alzheimer’s disease continuum: biological and methodological perspectives from disease heterogeneity

  • Rosaleena Mohanty,
  • Daniel Ferreira,
  • Agneta Nordberg,
  • Eric Westman,
  • for the Alzheimer’s Disease Neuroimaging Initiative

DOI
https://doi.org/10.1186/s13195-023-01173-1
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 16

Abstract

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Abstract Background Subtypes and patterns are defined using tau-PET (tau pathology) and structural MRI (atrophy) in Alzheimer’s disease (AD). However, the relationship between tau pathology and atrophy across these subtypes/patterns remains unclear. Therefore, we investigated the biological association between baseline tau-PET patterns and longitudinal atrophy in the AD continuum; and the methodological characterization of heterogeneity as a continuous phenomenon over the conventional discrete subgrouping. Methods In 366 individuals (amyloid-beta-positive cognitively normal, prodromal AD, AD dementia; amyloid-beta-negative cognitively normal), we examined the association between tau-PET patterns and longitudinal MRI. We modeled tau-PET patterns as a (a) continuous phenomenon with key dimensions: typicality and severity; and (b) discrete phenomenon by categorization into patterns: typical, limbic predominant, cortical predominant and minimal tau. Tau-PET patterns and associated longitudinal atrophy were contextualized within the Amyloid/Tau/Neurodegeneration (A/T/N) biomarker scheme. Results Localization and longitudinal atrophy change vary differentially across different tau-PET patterns in the AD continuum. Atrophy, a downstream event, did not always follow a topography akin to the corresponding tau-PET pattern. Further, heterogeneity as a continuous phenomenon offered an alternative and useful characterization, sharing correspondence with the conventional subgrouping. Tau-PET patterns also show differential A/T/N profiles. Conclusions The site and rate of atrophy are different across the tau-PET patterns. Heterogeneity should be treated as a continuous, not discrete, phenomenon for greater sensitivity. Pattern-specific A/T/N profiles highlight differential multimodal interactions underlying heterogeneity. Therefore, tracking multimodal interactions among biomarkers longitudinally, modeling disease heterogeneity as a continuous phenomenon, and examining heterogeneity across the AD continuum could offer avenues for precision medicine.

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