ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2016
Tissue-Plasminogen Activator Attenuates Alzheimer's Disease-Related Pathology Development in APPswe/PS1 Mice.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Pooled it
- Causal association of plasminogen activators and their inhibitors with Alzheimer's disease: a Mendelian randomization study.Archives of medical science : AMS · 2025Article
- Endothelial PDGF-D contributes to neurovascular protection after ischemic stroke by rescuing pericyte functions.Cellular and molecular life sciences : CMLS · 2024Article
- Mitochondrial dysfunction in chronic neuroinflammatory diseases (Review).International journal of molecular medicine · 2024Review
- The probable role of tissue plasminogen activator/neuroserpin axis in Alzheimer's disease: a new perspective.Acta neurologica Belgica · 2024Review
- Vascular Dysfunction in Alzheimer's Disease: Alterations in the Plasma Contact and Fibrinolytic Systems.International journal of molecular sciences · 2023Review
- Fibrin-Targeting Immunotherapy for Dementia.The journal of prevention of Alzheimer's disease · 2023Article
- Tissue Plasminogen Activator in Central Nervous System Physiology and Pathology: From Synaptic Plasticity to Alzheimer's Disease.Seminars in thrombosis and hemostasis · 2022Review
- Alzheimer's Disease: An Update and Insights Into Pathophysiology.Frontiers in aging neuroscience · 2022Review
- Hyperoxygenation Treatment Reduces Beta-amyloid Deposition via MeCP2-dependent Upregulation of MMP-2 and MMP-9 in the Hippocampus of Tg-APP/PS1 Mice.Experimental neurobiology · 2021Article
- Plasminogen Activators in Neurovascular and Neurodegenerative Disorders.International journal of molecular sciences · 2021Review
- The NGF Metabolic Pathway: New Opportunities for Biomarker Research and Drug Target Discovery : NGF Pathway Biomarkers and Drug Targets.Advances in experimental medicine and biology · 2021Article
- Drug Repurposing for Alzheimer's Disease Based on Protein-Protein Interaction Network.BioMed research international · 2021Article
- Multifocal Cerebral Microinfarcts Modulate Early Alzheimer's Disease Pathology in a Sex-Dependent Manner.Frontiers in immunology · 2021Article
- Spinosin Attenuates Alzheimer's Disease-Associated Synaptic Dysfunction via Regulation of Plasmin Activity.Biomolecules & therapeutics · 2020Article
- Canonical Wnt Pathway Maintains Blood-Brain Barrier Integrity upon Ischemic Stroke and Its Activation Ameliorates Tissue Plasminogen Activator Therapy.Molecular neurobiology · 2019Article
- Vascular Endothelial Growth Factor Isoform-B Stimulates Neurovascular Repair After Ischemic Stroke by Promoting the Function of Pericytes via Vascular Endothelial Growth Factor Receptor-1.Molecular neurobiology · 2018Article
- Can EGCG Alleviate Symptoms of Down Syndrome by Altering Proteolytic Activity?International journal of molecular sciences · 2018Review
- Sub-acute systemic erythropoietin administration reduces ischemic brain injury in an age-dependent manner.Oncotarget · 2016Article
- Severe chronic cerebral hypoperfusion induces microglial dysfunction leading to memory loss in APPswe/PS1 mice.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is the leading cause of dementia among elderly population. AD is characterized by the accumulation of beta-amyloid (Aβ) peptides, which aggregate over time to form amyloid plaques in the brain. Reducing soluble Aβ levels and consequently amyloid plaques constitute an attractive therapeutic avenue to, at least, stabilize AD pathogenesis. The brain possesses several mechanisms involved in controlling cerebral Aβ levels, among which are the tissue-plasminogen activator (t-PA)/plasmin system and microglia. However, these mechanisms are impaired and ineffective in AD. Here we show that the systemic chronic administration of recombinant t-PA (Activase rt-PA) attenuates AD-related pathology in APPswe/PS1 transgenic mice by reducing cerebral Aβ levels and improving the cognitive function of treated mice. Interestingly, these effects do not appear to be mediated by rt-PA-induced plasmin and matrix metalloproteinases 2/9 activation. We observed that rt-PA essentially mediated a slight transient increase in the frequency of patrolling monocytes in the circulation and stimulated microglia in the brain to adopt a neuroprotective phenotype, both of which contribute to Aβ elimination. Our study unraveled a new role of rt-PA in maintaining the phagocytic capacity of microglia without exacerbating the inflammatory response and therefore might constitute an interesting approach to stimulate the key populations of cells involved in Aβ clearance from the brain.
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Registered trials
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.