Pericapillary Haem-Rich Deposits: Evidence for Microhaemorrhages in Aging Human Cerebral Cortex
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In this Post mortem study, we examined haem-rich deposits (HRDs) in patients with and without dementia, using a histochemical label (Prussian blue) to show haem, autofluorescence to detect red blood cells (RBCs), and immunohistochemistry for clotting-related factors and collagen IV. The patients studied had no clinical or Post mortem evidence of macrovascular stroke. To allow examination of the spatial relationships between HRDs and the microvasculature, we cut 45-µm sections. Haem-rich deposits were small (< 200 µm diameter). They were rare in younger (< 50 years) patients but were more common in older (> 70 years) patients, particularly in cerebral cortex, and were most abundant in cases with senile plaques. Wherever HRDs appeared they were perivascular and appeared to form around capillaries or small arterioles. Using a software package (Proxan) developed to outline vessels and HRDs, and to analyse the distances between them, a tight spatial correlation between HRDs and capillaries was shown. In addition, HRDs were rich in von Willebrand factor (vWF), fibrinogen, collagen IV and RBCs. These observations suggest that HRDs are the residua of capillary bleeds (microhaemorrhages), and that microhaemorrhages are a common feature of the aging cerebral cortex, particularly where plaque pathology is present.
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Post mortem studies show vascular capillary leakages of blood-derived proteins in the prefrontal and entorhinal cortex and hippocampus of AD patients including perivascular accumulation of fibrin(ogen), thrombin, albumin, immunoglobulin G, and iron-containing proteins such as hemosiderin.
“Post mortem studies show vascular capillary leakages of blood-derived proteins in the prefrontal and entorhinal cortex and hippocampus of AD patients including perivascular accumulation of fibrin(ogen), thrombin, albumin, immunoglobulin G (IgG), and iron-containing proteins such as hemosiderin (120, 125, 230, 267, 412, 509, 527, 691).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [125]
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Experimental — accuracy not yet measuredRBC extravasation and brain infiltration by peripheral macrophages and neutrophils are reported in Alzheimer's disease post mortem studies.
“RBC extravasation (125) and brain infiltration by peripheral macrophages (175, 267) and neutrophils (676) are reported in AD post mortem studies”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [125]
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References 35 · Cited by 137
- Authors
- Cullen, K. M., Kócsi, Z., & Stone, J.
- Affiliations
- Australian National University (AU)
- Bendor Research Pty, Ltd, Sydney, NSW, Australia
- Corresponding author
- Cullen, Karen M
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2005-12
- Volume
- 25
- Issue
- 12
- Pages
- 1656-1667
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- OpenAlex
- W2089245103
- Cited by
- 137
- References
- 35
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 7 · 2023: 8 · 2022: 8 · 2021: 5 · 2020: 9 · 2019: 8 · 2018: 9 · 2017: 1 · 2016: 5 · 2015: 7 · 2014: 11 · 2013: 7 · 2012: 5
- FWCI
- 3.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- ANU Open Research (Australian National University) (submittedVersion)
- Funders
- Medical Research Council
- National Health and Medical Research Council
- National Medical Research Council
- Topics
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Keywords
- microhemorrhages, dementia, amyloid plaques, von Willebrand factor, fibrinogen, type IV collagen, erythrocytes, microcirculation, Alzheimer's disease pathology
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Capillaries, Cerebral Cortex, Cerebral Hemorrhage, Erythrocytes, Factor VIII, Female, Fibrinogen, Heme, Humans, Male, Middle Aged, Dementia, Vascular, Collagen Type IV
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