Cited by 209Barrier Structure and Function StudiesAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

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Differing associations between Aβ accumulation, hypoperfusion, blood–brain barrier dysfunction and loss of PDGFRB pericyte marker in the precuneus and parietal white matter in Alzheimer's disease

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Miners, J Scott, Schulz, Isabel, Love, Seth·2018·Journal of Cerebral Blood Flow & Metabolism

DOI 10.1177/0271678x17690761PMC PMC5757436

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Abstract

Recent studies implicate loss of pericytes in hypoperfusion and blood–brain barrier (BBB) leakage in Alzheimer's disease (AD). In this study, we have measured levels of the pericyte marker, platelet-derived growth factor receptor-β (PDGFRB), and fibrinogen (to assess blood–brain barrier leakage), and analyzed their relationship to indicators of microvessel density (von Willebrand factor level), ante-mortem oxygenation (myelin-associated glycoprotein:proteolipid protein-1 ratio and vascular endothelial growth factor level), Aβ level and plaque load, in precuneus and underlying white matter from 49 AD to 37 control brains. There was reduction in PDGFRB and increased fibrinogen in the precuneus in AD. These changes correlated with reduction in oxygenation and with plaque load. In the underlying white matter, increased fibrinogen correlated with reduced oxygenation, but PDGFRB level was unchanged. The level of platelet-derived growth factor-ββ (PDGF-BB), important for pericyte maintenance, was increased in AD but mainly in the insoluble tissue fraction, correlating with insoluble Aβ level. Loss of the PDGFRB within the precuneus in AD is associated with fibrinogen leakage and reduced oxygenation, and related to fibrillar Aβ accumulation. In contrast, fibrinogen leakage and reduced oxygenation of underlying white matter occur independently of loss of PDGFRB, perhaps secondary to reduced transcortical perfusion.

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Additional file 1 of Hippocampal capillary pericytes in post-stroke and vascular dementias and Alzheimer’s disease and experimental chronic cerebral hypoperfusion
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Additional file 5 of Hippocampal capillary pericytes in post-stroke and vascular dementias and Alzheimer’s disease and experimental chronic cerebral hypoperfusion
Hase, Y., Jobson, D., Cheong, J., Gotama, K. T., Maffei, L., Hase, M., Hamdan, A., Ding, R., Polivkoski, T., Horsburgh, K. J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26681311
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Additional file 2 of Higher angiotensin-converting enzyme 2 (ACE2) levels in the brain of individuals with Alzheimer’s disease
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Additional file 1 of Analysis of complement system and its related factors in Alzheimer’s disease
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Additional file 2 of Hippocampal capillary pericytes in post-stroke and vascular dementias and Alzheimer’s disease and experimental chronic cerebral hypoperfusion
Hase, Y., Jobson, D., Cheong, J., Gotama, K. T., Maffei, L., Hase, M., Hamdan, A., Ding, R., Polivkoski, T., Horsburgh, K. J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26681302
Additional file 4 of Hippocampal capillary pericytes in post-stroke and vascular dementias and Alzheimer’s disease and experimental chronic cerebral hypoperfusion
Hase, Y., Jobson, D., Cheong, J., Gotama, K. T., Maffei, L., Hase, M., Hamdan, A., Ding, R., Polivkoski, T., Horsburgh, K. J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26681308
Hippocampal Vascularization Patterns and Its Role in Vascular Impairment
Azedi, F., & Joghataei, M. T. (2026) · IntechOpen eBooks · doi:10.5772/intechopen.1011628

Authors: Miners, J. S., Schulz, I., & Love, S.
Affiliations: University of Bristol (GB)
Corresponding author: Love, Seth
ORCID: Miners, J Scott
Love, Seth
Venue: Journal of Cerebral Blood Flow & Metabolism
Publisher: SAGE Publications
Published: 2017-02-02
Volume: 38
Issue: 1
Pages: 103-115
ISSN: 0271-678X (ISSN-L)
1559-7016
DOI: 10.1177/0271678x17690761
PMC: PMC5757436
OpenAlex: W2583122146
Cited by: 208
References: 58
Citations by year: 2026: 11 · 2025: 17 · 2024: 35 · 2023: 36 · 2022: 26 · 2021: 27 · 2020: 20 · 2019: 22 · 2018: 11 · 2017: 3
FWCI: 7.63
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Journal of Cerebral Blood Flow & Metabolism (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Bristol Research (University of Bristol) (publishedVersion, other-oa)
Funders: Alzheimer's Society
British Heart Foundation (PG/10/47/28285)
Medical Research Council
Topics: Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: Alzheimer's disease, pericytes, PDGFRβ, PDGF-BB, fibrinogen, blood-brain barrier disruption, cerebral hypoperfusion, precuneus, parietal white matter, amyloid plaques, fibrillar amyloid-beta, microvessel density, von Willebrand factor, myelin-associated glycoprotein, PLP1, cerebral perfusion
MeSH terms: Aged, Aged, 80 and over, Alzheimer Disease, Blood-Brain Barrier, Brain, Capillary Permeability, Cerebrovascular Circulation, Female, Humans, Male, Biomarkers, Amyloid beta-Peptides, Pericytes, Receptor, Platelet-Derived Growth Factor beta, White Matter

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Differing associations between Aβ accumulation, hypoperfusion, blood–brain barrier dysfunction and loss of PDGFRB pericyte marker in the precuneus and parietal white matter in Alzheimer's disease

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