ArticleAging2023
Chronic kidney disease causes blood-brain barrier breakdown via urea-activated matrix metalloproteinase-2 and insolubility of tau protein.
Article in Aging, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 30 citations in OpenAlex.
- Comparative Analysis of Regional Blood-Brain Barrier Permeability in Humans and Rodents: An Evolutionary Perspective.Research square · 2026Article
- Microglial Ccl4-Ccr5 signaling links systemic inflammation to synaptic loss and memory deficits in chronic kidney disease.Journal of neuroinflammation · 2026Article
- Review
- The Role of Brain Structure in Explaining Physical Functioning in Male Veterans With Impaired Kidney Function.Journal of the American Geriatrics Society · 2026Article
- High-Phosphate-Induced Hypertension: The Pathogenic Role of Fibroblast Growth Factor 23 (FGF23) Signaling in Sympathetic Nervous System Activation.International journal of molecular sciences · 2026Review
- Relationship of Estimated Glomerular Filtration Rate (eGFR) and Neuron-Specific Enolase (NSE) with Cognitive Dysfunction in Type 2 Diabetes Mellitus: A Cross-Sectional Analysis.International journal of general medicine · 2026Article
- Structural brain changes, cerebral oxygenation, and cognitive function in hemodialysis patients: a cross-sectional study.Frontiers in medicine · 2026Article
- Advances in basic research on post-cardiac arrest syndrome in adults: a comprehensive review.Frontiers in medicine · 2026Review
- A guide to uraemic toxicity.Nature reviews. Nephrology · 2026Review
- Impact of kidney function on biomarkers of neurodegeneration, white matter hyperintensities, and cognition in older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Neuroprotective Effect of Rosuvastatin Calcium Combined with Hyperbaric Oxygen Mediated p38MAPK Pathway in Rats with Leukoaraiosis.Cell biochemistry and biophysics · 2025Article
- Claudin 5 Across the Vascular Landscape: From Blood-Tissue Barrier Regulation to Disease Mechanisms.Cells · 2025Review
- Drivers and mechanisms of cognitive decline in chronic kidney disease.Nature reviews. Nephrology · 2025Review
- Uremic Toxins, CKD, and Cognitive Dysfunction.Journal of the American Society of Nephrology : JASN · 2025Review
- N-Acetylcysteine Attenuates Aβ-Mediated Oxidative Stress, Blood-Brain Barrier Leakage, and Renal Dysfunction in 5xFAD Mice.International journal of molecular sciences · 2025Article
- The role of the intestinal microbiome in cognitive decline in patients with kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Dose-dependent association between estimated glomerular filtration rate and the subsequent risk of depression: An analysis of a nationwide epidemiological dataset.European journal of clinical investigation · 2025Article
- Reduced global BOLD-CSF coupling in chronic kidney disease-related cognitive impairment: a resting-state functional MRI study.Frontiers in neurology · 2025Article
- Cerebral blood flow following successful living kidney transplantation: the VINTAGE study.Clinical kidney journal · 2025Article
- Cognitive Impairment Related to Chronic Kidney Disease Is Associated with a Decreased Abundance of Membrane-Bound Klotho in the Cerebral Cortex.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic kidney disease (CKD) causes cognitive impairment and contributes to the overall global burden of dementia. However, mechanisms through which the kidneys and brain communicate are not fully understood. We established a CKD mouse model through adenine-induced tubulointerstitial fibrosis. Novel object recognition tests indicated that CKD decreased recognition memory. Sarkosyl-insoluble-proteomic analyses of the CKD mouse hippocampus revealed an accumulation of insoluble MAPT (microtubule-associated protein tau) and RNA-binding proteins such as small nuclear ribonucleoprotein U1 subunit 70 (SNRNP70). Additionally, there was an accumulation of Immunoglobulin G (IgG), indicating blood-brain barrier (BBB) breakdown. We identified that expressions of essential tight-junction protein claudin-5 and adherens-junction protein platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) were decreased in the brain endothelial cells of CKD mice. We determined urea as a major uremic solute that dose dependently decreased both claudin-5 and PECAM-1 expression in the mouse brain endothelial cell line bEnd.3 cells. Gelatin zymography indicated that the serum of CKD mice activated matrix metalloproteinase-2 (MMP2), while marimastat ameliorated the reduction of claudin-5 expression by urea in bEnd.3 cells. This study established a brain proteomic signature of CKD indicating BBB breakdown and insolubility of tau protein, which are pathologically linked to Alzheimer's disease. Urea-mediated activation of MMP2 was partly responsible for BBB breakdown in CKD.
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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.