Microvascular pathology in the aging human brain: Evidence that senile plaques are sites of microhaemorrhages

dc.contributor.authorCullen, Karen
dc.contributor.authorKocsi, Zoltan
dc.contributor.authorStone, Jonathan
dc.date.accessioned2015-12-08T22:40:20Z
dc.date.issued2006
dc.date.updated2015-12-08T10:22:48Z
dc.description.abstractAmyloid-rich plaques are a feature of the aging human cerebral cortex. We have recently described another feature of aging human cortex, microhaemorrhages, identified by their content of haem, red blood cells, collagen and clotting factors, and their spatial relationship to capillaries. Here we relate microhaemorrhages to amyloid deposits. Observations were made in three groups: patients with no history of dementia, patients with Alzheimer's disease (AD) and patients with Down's syndrome (DS) and dementia. Amyloid deposits and microhaemorrhages were labelled in adjacent sections, amyloid deposits with antibodies to β-amyloid (βA), and microhaemorrhages by Prussian blue histochemistry for haem. The densities and sizes of βA deposits and haem-rich deposits (HRDs), and their relationship to blood vessels, were surveyed in temporal, cingulate and superior frontal cortex. Our results suggest that HRDs and βA deposits are the same sites of pathology. Their densities in the cortex and white matter of the regions surveyed varied markedly between cases, particularly between demented and non-demented cases, but they always co-varied; where haem deposits were sparse or numerous, so were βA deposits. Both HRDs and βA deposits formed adjacent to or encircling small vessels, often at branch points, and a spatial proximity analysis confirmed that both were found close to or colocalising with microvessels. Both HRDs and βA deposits were associated with blood- or vessel-derived proteins (fibrinogen, von Willebrand factor and collagen VI). Since haem is an established marker of cerebral bleeding, and amyloid is a marker of senile plaques, our results indicate that senile plaques are sites of microhaemorrhages. This colocalisation raises the very testable questions of whether microhaemorrhages are early events in plaque formation and whether therapies which stabilise cerebral microvessels can prevent the onset or slow the progress of dementias associated with plaque formation.
dc.identifier.issn0197-4580
dc.identifier.urihttp://hdl.handle.net/1885/36458
dc.publisherElsevier
dc.sourceNeurobiology of Aging
dc.subjectKeywords: amyloid; amyloid beta protein; antibody; collagen type 6; ferric ferrocyanide; fibrinogen; heme; von Willebrand factor; adult; aged; aging; Alzheimer disease; article; brain hemorrhage; cingulate gyrus; clinical article; controlled study; dementia; Down s ?-Amyloid; Alzheimer's disease; Capillary; Collagen IV; Fibrinogen; Haem; Microhaemorrhage; Microvasculature; Senile plaques; von Willebrand factor
dc.titleMicrovascular pathology in the aging human brain: Evidence that senile plaques are sites of microhaemorrhages
dc.typeJournal article
local.bibliographicCitation.lastpage1796
local.bibliographicCitation.startpage1786
local.contributor.affiliationCullen, Karen, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationKocsi, Zoltan, Bendor Research Pty Ltd
local.contributor.affiliationStone, Jonathan, College of Medicine, Biology and Environment, ANU
local.contributor.authoremailrepository.admin@anu.edu.au
local.contributor.authoruidCullen, Karen, u4166599
local.contributor.authoruidStone, Jonathan, u4056002
local.description.embargo2037-12-31
local.description.notesImported from ARIES
local.identifier.absfor060104 - Cell Metabolism
local.identifier.ariespublicationu9204316xPUB136
local.identifier.citationvolume27
local.identifier.doi10.1016/j.neurobiolaging.2005.10.016
local.identifier.scopusID2-s2.0-33750000602
local.identifier.uidSubmittedByu9204316
local.type.statusPublished Version

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