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Updated: Jun 25, 2026

Abbiategrasso Brain Bank Protocol for Collecting, Processing and Characterizing Aging Brains
Published on: June 3, 2020
Cortical gray-white matter contrast alterations precede amyloid-β positivity and macrostructural changes in older
Leonard Pieperhoff1,2, Luigi Lorenzini1,2,3, Francisco Almeida4,5
1Department of Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam University Medical Center, Amsterdam, the Netherlands.
Introduction:
Early Alzheimer's disease (AD) involves subtle cortical changes that may precede atrophy. Magnetic resonance imaging (MRI) microstructural markers may detect earlier pathology than classical morphometry.
Methods:
We analyzed cross-sectional MRI and amyloid-β (Aβ) positron emission tomography (PET) data from 1323 non-demented AMYPAD participants. Cortical volume, thickness, gray-white matter contrast (GWC), and mean diffusivity (MD) were related to global Aβ burden and estimated time to Aβ-positivity using regression, correlation, and change-point analyses.
Results:
Microstructural measures showed stronger age associations than macrostructural measures, whereas all measures were unaffected by apolipoprotein E (APOE) -ε4 carriership. GWC and MD showed minimal overlap with volume and thickness. Higher Aβ burden was most strongly associated with reduced GWC and cortical thinning. Change-point analyses showed GWC alterations preceded Aβ-positivity by several years.
Discussion:
Cortical microstructural MRI, particularly GWC, changes earlier than atrophy and may serve as an early in vivo marker of AD pathology.
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