The DOI matches its Crossref record; 57 of the 58 references it cites were found in a registry or an index.
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
Open accessAbstract
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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“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 [412]
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“Pericyte loss has been confirmed by decreased levels of pericyte marker PDGFR 𝛃 in the precuneus (412) and loss of pericytes in the subcortical white matter (419).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [412]
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1 retracted
RETRACTED ARTICLE: Pericyte loss influences Alzheimer-like neurodegeneration in mice
Sagare, A. P., Bell, R. D., Zhao, Z., Ma, Q., Winkler, E. A., Ramanathan, A., & Zlokovic, B. V. (2013) · Nature Communications · doi:10.1038/ncomms3932 · Cited by 589
RetractedMontine, T. J., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., Mirra, S. S., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0910-3 · Cited by 2,894 · cited 1×
“In those from patients with AD, the diagnosis had been made according to the NIA-AA guidelines.(40) Control brains were from people with no 104 Journal of Cerebral Blood Flow & Metabolism 38(1)”
Blood-brain barrier breakdown in the aging human hippocampus
Montagne, A., Barnes, S. R., Sweeney, M. D., Halliday, M. R., Sagare, A. P., Zhao, Z., Toga, A. W., Jacobs, R. E., Liu, C. Y., Amezcua, L., et al. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.032 · Cited by 2,102
The role of pericytes in blood-vessel formation and maintenance
Bergers, G., & Song, S. (2005) · Neuro-Oncology · doi:10.1215/s1152851705000232 · Cited by 1,584
Bell, R. D., Winkler, E. A., Sagare, A. P., Singh, I., LaRue, B., Deane, R., & Zlokovic, B. V. (2010) · Neuron · doi:10.1016/j.neuron.2010.09.043 · Cited by 1,448
Cerebral microvascular pathology in aging and Alzheimer's disease
Farkas, E., & Luiten, P. G. M. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00068-x · Cited by 1,102
Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study
Ruitenberg, A., den Heijer, T., Bakker, S. L. M., van Swieten, J. C., Koudstaal, P. J., Hofman, A., & Breteler, M. M. B. (2005) · Annals of Neurology · doi:10.1002/ana.20493 · Cited by 733
Halliday, M. R., Rege, S. V., Ma, Q., Zhao, Z., Miller, C. A., Winkler, E. A., & Zlokovic, B. V. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2015.44 · Cited by 649
A role for VEGF as a negative regulator of pericyte function and vessel maturation
Greenberg, J. I., Shields, D. J., Barillas, S. G., Acevedo, L. M., Murphy, E. A., Huang, J., Scheppke, L., Stockmann, C., Johnson, R. S., Angle, N., et al. (2008) · Nature · doi:10.1038/nature07424 · Cited by 638
Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease
van de Haar, H. J., Burgmans, S., Jansen, J. F. A., van Osch, M. J. P., van Buchem, M. A., Muller, M., Hofman, P. A. M., Verhey, F. R. J., & Backes, W. H. (2016) · Radiology · doi:10.1148/radiol.2016152244 · Cited by 601
Research works printed but not linked: 6
- Chui HC, 2012, Alzheimers Research & Therapy, 4, 1
- Thomas TL, 2015, Neuropathol Appl Neurobiol, 41, 22
- Sagare AP, 2013, Nat Commun, 4
- Lorberboym M, 2003, J Nucl Med, 44, 1898
- Miners JS, Brain Pathol
- 10.1111/nan.12188 · DOI
Cited by
Sorted by citations
Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders
Sweeney, M. D., Sagare, A. P., & Zlokovic, B. V. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.188 · Cited by 3,076
Blood-Brain Barrier: From Physiology to Disease and Back
Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2019) · Physiological Reviews · doi:10.1152/physrev.00050.2017 · Cited by 2,312
The blood-brain barrier in aging and neurodegeneration
Knox, E. G., Aburto, M. R., Clarke, G., Cryan, J. F., & O’Driscoll, C. M. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01511-z · Cited by 738
Fibrinogen in neurological diseases: mechanisms, imaging and therapeutics
Petersen, M. A., Ryu, J. K., & Akassoglou, K. (2018) · Nature reviews. Neuroscience · doi:10.1038/nrn.2018.13 · Cited by 527
Role of Blood-Brain Barrier in Alzheimer’s Disease
Cai, Z., Qiao, P.-F., Wan, C.-Q., Cai, M., Zhou, N.-K., & Li, Q. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-180098 · Cited by 370
Metadata
- Authors
- Miners, J. S., Schulz, I., & Love, S.
- Affiliations
- University of Bristol (GB)
- Corresponding author
- 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
- 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
- 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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