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dc.contributor.author
Kirabali, Tunahan
dc.contributor.author
Rust, Ruslan
dc.contributor.author
Rigotti, Serena
dc.contributor.author
Siccoli, Alessandro
dc.contributor.author
Nitsch, Roger M.
dc.contributor.author
Kulic, Luka
dc.date.accessioned
2020-12-21T17:06:42Z
dc.date.available
2020-10-01T07:15:13Z
dc.date.available
2020-10-02T06:04:34Z
dc.date.available
2020-10-02T06:05:34Z
dc.date.available
2020-12-21T17:06:42Z
dc.date.issued
2020-11
dc.identifier.issn
1015-6305
dc.identifier.issn
1750-3639
dc.identifier.other
10.1111/bpa.12895
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/443800
dc.description.abstract
In the brain capillaries, endothelial cells, pericytes, astrocytes and microglia form a structural and functional complex called neurovascular unit (NVU) which is critically involved in maintaining neuronal homeostasis. In the present study, we applied a comprehensive immunohistochemical approach to investigate the structural alterations in the NVU across different Alzheimer's disease (AD) neuropathological stages. Post-mortem human cortical and hippocampal samples derived from AD patients and non-demented elderly control individuals were immunostained using a panel of markers representing specific components of the NVU including Collagen IV (basement membrane), PDGFR-beta (pericytes), GFAP (astrocytes), Iba1 (microglia), MRC1 (perivascular macrophages) and lectin as an endothelial cell label. Astrocytes (GFAP) and microglia (Iba1) were quantified both in the whole visual-field and specifically within the NVU, and the sample set was additionally analyzed using anti-tau (AT8) and three different anti-A beta (clones G2-10, G2-11, 4G8) antibodies. Analyses of lectin labeled sections showed an altered vascular distribution in AD patients as revealed by a reduced nearest distance between capillaries. Within the NVU, a Braak-stage dependent reduction in pericyte coverage was identified as the earliest structural alteration during AD progression. In comparison to non-demented elderly controls, AD patients showed a significantly higher astrocyte coverage within the NVU, which was paralleled by a reduced microglial coverage around capillaries. Assessment of perivascular macrophages moreover demonstrated a relocation of these cells from leptomeningeal arteries to penetrating parenchymal vessels in AD patients. Collectively, the results of our study represent a comprehensive first in-depth analysis of AD-related structural changes in the NVU and suggest distinct alterations in all components of the NVU during AD progression.
en_US
dc.language.iso
en
en_US
dc.publisher
Wiley
en_US
dc.subject
GFAP
en_US
dc.subject
Iba1
en_US
dc.subject
PDGFR‐β
en_US
dc.subject
MRC1
en_US
dc.subject
NVU
en_US
dc.subject
vascular dysfunction
en_US
dc.title
Distinct changes in all major components of the neurovascular unit across different neuropathological stages of Alzheimer's disease
en_US
dc.type
Journal Article
dc.date.published
2020-08-31
ethz.journal.title
Brain Pathology
ethz.journal.volume
30
en_US
ethz.journal.issue
6
en_US
ethz.journal.abbreviated
Brain Pathol
ethz.pages.start
1056
en_US
ethz.pages.end
1070
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Oxford
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2020-10-01T07:15:23Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Metadata only
en_US
ethz.rosetta.installDate
2020-10-02T06:04:44Z
ethz.rosetta.lastUpdated
2021-02-15T22:47:08Z
ethz.rosetta.versionExported
true
ethz.COinS
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