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T1-weighted/T2-weighted ratio reflects microstructural changes in Alzheimer's disease

N Reijner1,2, M Riscado Ramos3, E Jacobs3

  • 1Department of Anatomy and Neurosciences, Section Clinical Neuroanatomy and Biobanking, Amsterdam UMC, De Boelelaan 1108, Amsterdam, 1081 HZ, The Netherlands. n.reijner@amsterdamumc.nl.

Alzheimer'S Research & Therapy
|May 28, 2026
PubMed
Abstract

Insights

The T1-weighted/T2-weighted ratio (T1w/T2w-ratio) is not solely a myelin marker in Alzheimer's disease (AD). It reflects broader microstructural changes, including amyloid-beta, tau pathology, and neuro-axonal damage, making it a valuable tool for tracking AD progression.

Area of Science:

  • Neuroimaging
  • Neuropathology
  • Biomarker Discovery

Background:

  • The T1-weighted/T2-weighted ratio (T1w/T2w-ratio) is a neuroimaging technique used to assess myelin content.
  • Its utility may extend beyond myelin to reflect broader microstructural integrity changes.
  • This study investigates the T1w/T2w-ratio's ability to detect microstructural changes in Alzheimer's disease (AD).

Purpose of the Study:

  • To evaluate the T1w/T2w-ratio's capability in detecting microstructural alterations in the context of Alzheimer's disease.
  • To determine if the T1w/T2w-ratio is specific to myelin or indicative of other pathological changes in AD.

Main Methods:

  • Postmortem and antemortem MRI scans from control and AD brain donors were analyzed.
  • T1w/T2w-ratio images were generated and parcellated using the Brainnetome atlas.
  • Immunohistochemistry was performed to quantify amyloid-beta, tau, neuro-axonal damage, myelin, microglia, and iron.

Main Results:

  • The T1w/T2w-ratio was significantly lower in AD brains compared to controls.
  • A strong correlation was observed between antemortem and postmortem T1w/T2w-ratios.
  • In AD, T1w/T2w-ratio correlated with myelin, microglia, amyloid-beta, phosphorylated tau, and neuro-axonal damage, but not iron.

Conclusions:

  • The T1w/T2w-ratio is associated with myelin density in controls but reflects broader microstructural integrity in AD.
  • It is not a myelin-specific marker in AD but correlates with key AD pathologies.
  • The T1w/T2w-ratio can serve as a valuable neuroimaging tool for tracking longitudinal microstructural changes in AD when interpreted with other biomarkers.
Keywords:
HeterogeneityHistologyImagingNeurodegenerationPathologyPhenotypeSubtype

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