ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2020
tPA Deficiency Underlies Neurovascular Coupling Dysfunction by Amyloid-β.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 57 citations in OpenAlex.
- Knockdown of endothelial Serpine1 improves stroke recovery by attenuating peri-infarct blood flow and blood-brain barrier disruption.Cell death & disease · 2026Article
- Endothelial PAI-1 Drives Lead-Induced Cerebral Amyloid Angiopathy via Activation of C3Biology · 2026Article
- Prolonged systemic inflammation worsens impairments to astrocyte CabioRxiv : the preprint server for biology · 2025Article
- High-caloric intake rescues early symptomatic AD-induced hippocampal neurovascular coupling deficits.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Mitochondrial connection to Alzheimer's disease and heart failure.Current opinion in physiology · 2025Article
- Neural circuit mechanisms underlying aberrantly prolonged functional hyperemia in young Alzheimer's disease mice.Molecular psychiatry · 2025Article
- Endothelium glutamate receptors in brain pathology.Frontiers in pharmacology · 2025Review
- Cerebrovascular alterations in a mouse model of late-onset Alzheimer's disease.Neurophotonics · 2025Article
- Causal association of plasminogen activators and their inhibitors with Alzheimer's disease: a Mendelian randomization study.Archives of medical science : AMS · 2025Article
- A cell-autonomous role for border-associated macrophages in ApoE4 neurovascular dysfunction and susceptibility to white matter injury.Nature neuroscience · 2024Article
- Lead Acetate Exposure and Cerebral Amyloid Accumulation: Mechanistic Evaluations in APP/PS1 Mice.Environmental health perspectives · 2024Article
- Cellular and molecular mechanisms of the blood-brain barrier dysfunction in neurodegenerative diseases.Fluids and barriers of the CNS · 2024Review
- The probable role of tissue plasminogen activator/neuroserpin axis in Alzheimer's disease: a new perspective.Acta neurologica Belgica · 2024Review
- Article
- Cerebrovascular Dysfunction in Alzheimer's Disease and Transgenic Rodent Models.Journal of experimental neurology · 2024Article
- Pharmacological inhibition of plasminogen activator inhibitor-1 prevents memory deficits and reduces neuropathology in APP/PS1 mice.Psychopharmacology · 2023Article
- Extracellular Vesicle-Serpine-1 Affects Neural Progenitor Cell Mitochondrial Networks and Synaptic Density: Modulation by Amyloid Beta and HIV-1.Molecular neurobiology · 2023Article
- Border-associated macrophages promote cerebral amyloid angiopathy and cognitive impairment through vascular oxidative stress.Molecular neurodegeneration · 2023Article
- Current views on meningeal lymphatics and immunity in aging and Alzheimer's disease.Molecular neurodegeneration · 2023Review
- Cell autonomous role of border associated macrophages in ApoE4 neurovascular dysfunction and susceptibility to white matter injury.Research square · 2023Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The amyloid-β (Aβ) peptide, a key pathogenic factor in Alzheimer's disease, attenuates the increase in cerebral blood flow (CBF) evoked by neural activity (functional hyperemia), a vital homeostatic response in which NMDA receptors (NMDARs) play a role through nitric oxide, and the CBF increase produced by endothelial factors. Tissue plasminogen activator (tPA), which is reduced in Alzheimer's disease and in mouse models of Aβ accumulation, is required for the full expression of the NMDAR-dependent component of functional hyperemia. Therefore, we investigated whether tPA is involved in the neurovascular dysfunction of Aβ. tPA activity was reduced, and the tPA inhibitor plasminogen inhibitor-1 (PAI-1) was increased in male mice expressing the Swedish mutation of the amyloid precursor protein (tg2576). Counteracting the tPA reduction with exogenous tPA or with pharmacological inhibition or genetic deletion of PAI-1 completely reversed the attenuation of the CBF increase evoked by whisker stimulation but did not ameliorate the response to the endothelium-dependent vasodilator acetylcholine. The tPA deficit attenuated functional hyperemia by suppressing NMDAR-dependent nitric oxide production during neural activity. Pharmacological inhibition of PAI-1 increased tPA activity, prevented neurovascular uncoupling, and ameliorated cognition in 11- to 12-month-old tg2576 mice, effects associated with a reduction of cerebral amyloid angiopathy but not amyloid plaques. The data unveil a selective role of the tPA in the suppression of functional hyperemia induced by Aβ and in the mechanisms of cerebral amyloid angiopathy, and support the possibility that modulation of the PAI-1-tPA pathway may be beneficial in diseases associated with amyloid accumulation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.