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Updated: Apr 5, 2026
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Published on: March 7, 2019
No neuropathological evidence for a direct topographical relation between microbleeds and cerebral amyloid angiopathy
Enikö Kövari1, Andreas Charidimou2, François R Herrmann3
1Department of Mental Health and Psychiatry, University Hospitals and University of Geneva, 2, chemin du Petit-Bel-Air, 1225, Geneva, Switzerland. eniko.kovari@hcuge.ch.
Introduction:
Cerebral microbleeds correspond to blood breakdown products, including hemosiderin-containing macrophages around small vessels on histological examination. Superficial lobar cerebral microbleeds are increasingly recognized on MRI as a biomarker of cerebral amyloid angiopathy but the direct association between amyloid-laden vessels burden and cerebral microbleeds has yet to be validated neuropathologically. To address this issue, we examined the frequency of histopathologically-defined cerebral microbleeds in different brain regions and their relationship with cerebral amyloid angiopathy in a large autopsy population.
Results:
The frontal, parietal and occipital cortex as well as the adjacent white matter and basal ganglia of 113 consecutive autopsies were examined. Cerebral microbleedss were identified on haematoxylin-eosin-stained histological slides, cerebral amyloid angiopathy using anti-amyloid antibody. Cerebral microbleeds were present in 92.9 % of the cases and cerebral amyloid angiopathy in 44.3 % of them. Cerebral microbleeds were more frequent in parietal and frontal lobes followed by the occipital region and basal ganglia. In contrast, cerebral amyloid angiopathy was most frequent in the occipital lobe. There was no significant topographical association between cerebral amyloid angiopathy presence or severity and cerebral microbleeds in any brain region. In lobar areas, cerebral amyloid angiopathy was found in the cortex, predominantly affecting pial arteries and their superficial cortical branches, in contrast to microbleeds which were mainly in the white matter and occurred around deeper arteries and arterioles, including the subcortical segment of long penetrating branches of pial vessels.
Conclusions:
Our study does not support a direct relation between cerebral microbleeds and cerebral amyloid angiopathy burden at the neuropathological level, raising intriguing questions on the potential pathophysiological mechanisms of cerebral microbleeds in the context of cerebral amyloid angiopathy or other small vessel disease pathology.
Insights
This study found no direct link between cerebral amyloid angiopathy and cerebral microbleeds in autopsy brains. Further research is needed to understand the causes of these microbleeds.
Area of Science:
- Neuropathology
- Cerebrovascular Diseases
- Neuroimaging Biomarkers
Background:
- Cerebral microbleeds (CMBs) are indicators of bleeding in the brain, often linked to cerebral amyloid angiopathy (CAA).
- CAA is associated with amyloid-laden vessels, but its direct relationship with CMBs requires neuropathological validation.
- Understanding this association is crucial for interpreting MRI findings and diagnosing small vessel diseases.
Purpose of the Study:
- To investigate the neuropathological association between cerebral amyloid angiopathy burden and histopathologically-defined cerebral microbleeds.
- To examine the frequency and topographical distribution of CMBs and CAA in a large autopsy cohort.
- To determine if CAA severity correlates with CMBs in specific brain regions.
Main Methods:
- Examination of 113 consecutive autopsies, analyzing frontal, parietal, and occipital cortex, white matter, and basal ganglia.
- Histopathological identification of CMBs using hematoxylin-eosin staining.
- Assessment of CAA using anti-amyloid antibody staining.
Main Results:
- CMBs were found in 92.9% of cases, while CAA was present in 44.3%.
- CMBs were most frequent in parietal and frontal lobes, whereas CAA was most prevalent in the occipital lobe.
- No significant topographical association was observed between CAA and CMBs; CMBs occurred deeper in the white matter, while CAA affected superficial cortical vessels.
Conclusions:
- The study did not find a direct neuropathological relationship between CAA burden and CMBs.
- These findings challenge the assumption of a direct link and suggest other mechanisms may underlie CMBs in CAA.
- Further research is warranted to elucidate the complex pathophysiology of CMBs in the context of small vessel diseases.
