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Updated: Feb 24, 2026
Visualization of Amyloid β Deposits in the Human Brain with Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry
Published on: March 7, 2019
Perilesional white matter gradients reveal microstructural differences in cerebral amyloid angiopathy versus
Xinyuan Yang1, Junfang Zhang2, Fang Xie3
1Department of Neurology & Institute of Neurology, Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Introduction:
White matter hyperintensities (WMHs) are common in both Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA), yet their spatial tissue characteristics and microstructural differences remain poorly understood.
Methods:
We analyzed 351 participants: 184 amyloid beta (Aβ)-positive AD and mild cognitive impairment (MCI), 139 Aβ-negative cognitively normal controls (CN), and 28 probable CAA. Multimodal magnetic resonance imaging metrics were used to estimate spatial gradient parameters for periventricular WMHs (pWMH) and deep WMHs (dWMH).
Results:
CAA demonstrated distinctive free-water fraction (FWF), fractional anisotropy (FA), mean diffusivity (MD), and plasma volume within pWMH, as well as spatial gradient parameters of pWMH. These pWMH spatial gradient parameters produced area under the curve (AUC) values of 0.71 (FWF), 0.72 (MD), and 0.79 (FA) when distinguishing CAA from AD/MCI. We retested a subset of the cohort after 1 to 2 years (AUCs: FWF = 0.89, MD = 0.79, FA = 0.85).
Discussion:
Spatial gradient parameters reflect disease-specific microstructural and vascular changes, providing insights into CAA and AD pathology.
Insights
Spatial gradient parameters in white matter hyperintensities (WMHs) can differentiate cerebral amyloid angiopathy (CAA) from Alzheimer's disease (AD). These microstructural and vascular changes offer new insights into neurodegenerative disease pathology.
Area of Science:
- Neuroimaging
- Neuropathology
- Biomarkers
Background:
- White matter hyperintensities (WMHs) are prevalent in Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA).
- Distinct spatial and microstructural characteristics of WMHs in these conditions are not well understood.
- Understanding these differences is crucial for accurate diagnosis and disease differentiation.
Purpose of the Study:
- To investigate the spatial tissue characteristics and microstructural differences of WMHs in AD and CAA.
- To identify imaging markers that can distinguish between CAA and AD/mild cognitive impairment (MCI).
Main Methods:
- Analysis of 351 participants: 184 amyloid beta (Aβ)-positive AD/MCI, 139 Aβ-negative cognitively normal controls (CN), and 28 probable CAA.
- Utilized multimodal magnetic resonance imaging (MRI) metrics to assess spatial gradient parameters of periventricular WMHs (pWMH) and deep WMHs (dWMH).
Main Results:
- Cerebral amyloid angiopathy (CAA) showed distinct free-water fraction (FWF), fractional anisotropy (FA), mean diffusivity (MD), and plasma volume in pWMH.
- pWMH spatial gradient parameters, particularly FA, effectively distinguished CAA from AD/MCI (AUC=0.79).
- Longitudinal analysis in a subset confirmed the robustness of these imaging markers (e.g., FA AUC=0.85).
Conclusions:
- Spatial gradient parameters of WMHs reflect disease-specific microstructural and vascular alterations.
- These findings provide valuable insights into the distinct pathologies of CAA and AD.
- Advanced MRI techniques can aid in differentiating neurodegenerative conditions based on WMH characteristics.
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