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Biomarkers.

Leonard Pieperhoff1, Luigi Lorenzini1, Mario Tranfa1,2

  • 1Amsterdam University Medical Center (Amsterdam UMC), Amsterdam, North Holland, Netherlands.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

Alzheimer's disease research often assumes a single amyloid-beta accumulation pattern. This study reveals five distinct cortical patterns of amyloid-PET signal, offering new insights into Alzheimer's disease heterogeneity.

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Area of Science:

  • Neuroimaging
  • Biomarkers
  • Alzheimer's Disease Research

Background:

  • Current Alzheimer's disease (AD) research often assumes a singular trajectory for cortical amyloid-beta (Aβ) accumulation.
  • However, amyloid positron emission tomography (PET) studies indicate the existence of multiple accumulation patterns, suggesting significant heterogeneity in AD progression.

Purpose of the Study:

  • To characterize the heterogeneity of Alzheimer's disease (AD) by employing independent spatial component analysis on amyloid-PET data.
  • To identify distinct spatial patterns of amyloid-beta (Aβ) deposition in the brain.

Main Methods:

  • Utilized spatial group-level independent component analysis (gICA) on amyloid-PET scans from two radiotracers ([18F]Flutemetamol and [18F]Florbetaben) in non-demented older individuals.
  • Optimized gICA dimensionality by maximizing spatial cross-correlations between radiotracers.
  • Investigated relationships between identified components, global Aβ burden (Centiloid), and regional gray matter (GM) volumes.

Main Results:

  • Identified five distinct cortical components (frontal, parietal, occipital, left temporal, right temporal) and four non-cortical components.
  • Cortical components showed strong positive associations with global Aβ burden (Centiloid), while non-cortical components had minimal association.
  • Cortical component loading, particularly in temporal regions, was negatively associated with gray matter volume, while other components showed positive associations.

Conclusions:

  • Demonstrated five cortical and four non-cortical independent components of amyloid-PET signal with high cross-tracer consistency.
  • These components exhibit differential relationships with gray matter volumes, highlighting the potential for capturing heterogeneous disease processes in Alzheimer's disease.