Pericyte degeneration leads to neurovascular uncoupling and limits oxygen supply to brain
Open accessAbstract
Pericytes are perivascular mural cells of brain capillaries. They are positioned centrally in the neurovascular unit between endothelial cells, astrocytes and neurons. This position allows them to regulate key neurovascular functions of the brain. The role of pericytes in the regulation of cerebral blood flow (CBF) and neurovascular coupling remains, however, under debate. Using loss-of-function pericyte-deficient mice, here we show that pericyte degeneration diminishes global and individual capillary CBF responses to neuronal stimuli, resulting in neurovascular uncoupling, reduced oxygen supply to the brain and metabolic stress. Neurovascular deficits lead over time to impaired neuronal excitability and neurodegenerative changes. Thus, pericyte degeneration as seen in neurological disorders such as Alzheimer's disease may contribute to neurovascular dysfunction and neurodegeneration associated with human disease.
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Amyloid-induced vascular constriction, increased vascular resistance, and degeneration of pericytes may further contribute to hypoperfusion.
“Amyloid-induced vascular constriction, increased vascular resistance, and degeneration of pericytes may further contribute to hypoperfusion (Kisler et al., 2017; Yew et al., 2017).”
From White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease (2018) · cites this paper as Kisler et al., 2017
The Discussion reports that pericyte degeneration reduces cerebral blood-flow responses and oxygen supply, and may contribute to neurovascular dysfunction in disorders such as Alzheimer’s disease. The cited paper does not establish the sentence’s separate claims about amyloid-induced vascular constriction or increased vascular resistance. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn the case of Pdgfrß deficiency, blood-brain barrier breakdown and vascular phenotype precede neuronal degeneration and loss.
“In the case of Pdgfrß deficiency, BBB breakdown and vascular phenotype precede neuronal degeneration and loss (59, 319, 650), whereas pericyte-deficient Pdgfb ret/ret mice develop deep brain calcification at a later age resembling IBGC (309).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [319]
The Results (‘Impaired neuronal function and secondary neurodegeneration’; page unavailable) show vascular-flow abnormalities in 1–2-month-old Pdgfrβ+/− mice without detectable neuronal loss, followed by neuronal loss at 6–8 months. The Discussion mentions blood–brain barrier breakdown as a possible contributor to later neurodegeneration, but does not establish when the barrier breaks down relative to neuronal loss. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIn the mammalian brain, cerebral arteries, arterioles, and capillaries supply CNS circuits with blood in response to neuronal stimuli by increasing the rate of CBF and oxygen delivery, a mechanism known as neurovascular coupling.
“In the mammalian brain, cerebral arteries, arterioles, and capillaries supply CNS circuits with blood in response to neuronal stimuli by increasing the rate of CBF and oxygen delivery, a mechanism known as neurovascular coupling (271, 319).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [319]
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“Amyloid-induced vascular constriction, increased vascular resistance, and degeneration of pericytes may further contribute to hypoperfusion (Kisler et al., 2017; Yew et al., 2017).”
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- Authors
- Kisler, K., Nelson, A. R., Rege, S. V., Ramanathan, A., Wang, Y., Ahuja, A., Lazic, D., Tsai, P. S., Zhao, Z., Zhou, Y., Boas, D. A., Sakadžić, S., & Zlokovic, B. V.
- Affiliations
- University of Southern California (US)
- University of California San Diego (US)
- Army Medical University (CN)
- Harvard University (US)
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2017-01-30
- Volume
- 20
- Issue
- 3
- Pages
- 406-416
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC5323291
- OpenAlex
- W2582407848
- Cited by
- 497
- References
- 65
- Citations by year
- 2026: 46 · 2025: 38 · 2024: 53 · 2023: 39 · 2022: 58 · 2021: 62 · 2020: 76 · 2019: 57 · 2018: 43 · 2017: 23
- FWCI
- 27.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- OpenBU (Boston University) (submittedVersion)
- Funders
- National Institute on Aging (R01AG023084, R01AG039452, P50AG005142, RF1AG039452, P01AG052350)
- National Institute of Mental Health (R01MH111359)
- National Institute of Neurological Disorders and Stroke (R24NS092986, P01NS055104, R01NS100459, R01NS034467, R01NS091230)
- National Institute of Biomedical Imaging and Bioengineering (R01EB000790, R01EB021018)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- pericytes, pericyte degeneration, neurovascular uncoupling, cerebral blood flow, cerebral oxygenation, neurovascular unit, capillary blood flow, neuronal excitability, neurodegeneration, Alzheimer's disease
- MeSH terms
- Animals, Brain, Capillaries, Female, Male, Mice, Transgenic, Nerve Degeneration, Neurons, Oxygen, Stress, Physiological, Vasodilation, Cell Death, Homeodomain Proteins, Pericytes, Receptor, Platelet-Derived Growth Factor beta, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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