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Related Experiment Video

Updated: Aug 7, 2025

Whole-brain Segmentation and Change-point Analysis of Anatomical Brain MRI—Application in Premanifest Huntington's Disease
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Exploring the ATN classification system using brain morphology.

Nils Heinzinger1,2, Anne Maass3,4, David Berron3,4

  • 1German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany. nils.heinzinger@st.ovgu.de.

Alzheimer'S Research & Therapy
|March 14, 2023
PubMed
Summary
This summary is machine-generated.

Early amyloid biomarker changes precede tau and neurodegeneration, driving brain volume loss in Alzheimer's disease (AD) progression. The amyloid cascade hypothesis aligns with medial temporal lobe atrophy patterns.

Keywords:
ATNAlzheimer’s diseaseAmyloidBiomarkerMRIMemoryVBMVoxel-based morphometry

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Area of Science:

  • Neuroimaging
  • Biomarker Discovery
  • Neurodegenerative Diseases

Background:

  • The amyloid-tau-neurodegeneration (ATN) framework classifies Alzheimer's disease (AD) biomarkers.
  • The amyloid cascade hypothesis (ACH) posits a specific progression of biomarker changes (A-T-N).

Purpose of the Study:

  • To assess evidence for monotonic brain volume decline across different ATN progression sequences.
  • To compare the ACH sequence with alternative biomarker transition pathways.

Main Methods:

  • Utilized voxel-based morphometry (VBM) on MRI data from the DELCODE cohort (n=437).
  • Classified participants using CSF amyloid-beta (A), CSF phospho-tau (T), and hippocampal volume/CSF total-tau (N).
  • Compared Bayesian Information Criterion evidence for various monotonic gray matter volume decline sequences.

Main Results:

  • The ACH sequence (A-T-N-➔A+T-N-➔A+T+N-➔A+T+N+) showed consistency with cognitive decline and clinical diagnosis.
  • Early amyloid conversion before tau/neurodegeneration (ACH/ANT) was associated with volume loss in 65% of gray matter.
  • Medial temporal lobe regions showed stronger volume decline evidence, consistent with early tau deposition.

Conclusions:

  • Early amyloid status conversion precedes tau and neurodegeneration, correlating with observed brain volume loss in AD.
  • The ATN system and ACH are compatible with monotonic medial temporal lobe (MTL) atrophy progression.