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Updated: Apr 28, 2026
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Longitudinal In Vivo Imaging of the Cerebrovasculature: Relevance to CNS Diseases
Published on: December 6, 2016
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Vascular Microbleeds Without Brain Atrophy: A Microvascular Signature of Mid-Stage 5xFAD Pathology
Xiuli Yang1, Yuguo Li1,2, Adnan Bibic2
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Biorxiv : the Preprint Server for Biology
|December 22, 2025
Summary
Cerebral microbleeds specifically indicate vascular injury from amyloid in Alzheimer's disease (AD). This finding highlights microbleeds as a key biomarker for diagnosing AD-related vascular fragility.
Area of Science:
- Neurology
- Neuroimaging
- Vascular Biology
Background:
- Cerebral microbleeds are linked to vascular injury in Alzheimer's disease (AD).
- Cerebral amyloid angiopathy (CAA) is a primary cause of microbleeds in AD.
- Distinguishing microbleed causes is crucial for AD diagnosis and treatment.
Purpose of the Study:
- To determine if microbleeds are specific to amyloid-related vascular injury.
- To compare microbleed pathology in an AD mouse model (5xFAD) versus a small-vessel disease (SVD) model.
- To validate imaging findings with ex vivo scans.
Main Methods:
- Utilized multimodal MRI (gradient-echo, spin-echo, diffusion-weighted imaging) in vivo.
- Employed high-resolution ex vivo anatomical scans for validation.
- Compared the 5xFAD amyloidosis model with an SVD model featuring smooth-muscle cell loss.
Main Results:
- Gradient-echo MRI detected hippocampal microbleeds in 5xFAD mice, absent in the SVD model.
- No blood-brain barrier disruption was observed in the SVD cohort.
- Diffusion-weighted MRI revealed region-specific changes in the midbrain of 5xFAD mice.
Conclusions:
- Microbleeds are a pathology-specific marker of amyloid-related vascular injury.
- Imaging evidence supports microbleeds as a biomarker for amyloid-driven vascular fragility in AD.
- Microbleeds can refine diagnostic and therapeutic strategies for Alzheimer's disease.
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