ArticleTranslational psychiatry2024
Elevated CSF angiopoietin-2 correlates with blood-brain barrier leakiness and markers of neuronal injury in early Alzheimer's disease.
Article in Translational psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- GWAS meta-analysis of cerebrospinal fluid Alzheimer's biomarkers reveals loci regulating lipids, brain volume and autophagy.Nature communications · 2026Pooled it
- Dysregulated TIE-2 expression is associated with blood-brain barrier leakiness and Alzheimer's disease-related neuropathology.Brain pathology (Zurich, Switzerland) · 2026Article
- "Morphological, Functional, and Molecular Progression of Blood-Brain Barrier Dysfunction in Alzheimer's Disease".Journal of molecular neuroscience : MN · 2026Review
- Dysregulated TIE-2 expression in Alzheimer's disease: Further considerations on regional specificity and shedding evidence.Brain pathology (Zurich, Switzerland) · 2026Article
- New perspectives on VEGF signalling in Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2026Review
- Review
- Evaluation of Soluble Triggering Receptor Expressed on Myeloid Cells 2 (sTREM2) in Cerebrospinal Fluid, Serum, and Plasma Using the Fully Automated Lumipulse Platform.Journal of clinical laboratory analysis · 2026Article
- Elevated levels of circulating plasma sPDGFRβ in cognitively impaired APOE4 carriers.GeroScience · 2026Article
- Dysfunction of the neurovascular unit as a temporal driver in Alzheimer's pathogenesis.Translational neurodegeneration · 2026Review
- MultiGEOmics: Graph-Based Integration of Multi-Omics via Biological Information Flows.bioRxiv : the preprint server for biology · 2026Article
- Angiopoietin-2 aggravates Alzheimer's disease by promoting blood-brain barrier dysfunction and neuroinflammation.Cell reports · 2026Article
- Microvesicles, exosomes and their combinations with cytoplasmic organelles: from their discovery to their innovative roles in clinical medicine.Biology direct · 2026Review
- Brain Endothelial Glycocalyx as a Blood-Facing Translational Interface in Alzheimer's Disease: Beyond "Leaky" Barriers Toward Repair-First Stratification.Drug design, development and therapy · 2026Review
- Breaking the resistance barrier: synergistic evolution of CAR-T cells and bispecific antibodies in the era of precision immuno-oncology.Frontiers in immunology · 2026Review
- Remodeling of the brain immune microenvironment in Alzheimer's disease: interactions among microglia, astrocytes, complement, and the neurovascular unit.Frontiers in immunology · 2026Review
- Blood-brain barrier dysfunction and peripheral immune activation in Alzheimer's disease: an inflammation-centered review.Frontiers in immunology · 2026Review
- Development of Plasma Protein Classification Models for Alzheimer's Disease Using Multiple Machine Learning Approaches.International journal of molecular sciences · 2025Article
- CSF markers of vascular injury correlate with tau and cognitive decline in early Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- MAPK signaling and angiopoietin-2 contribute to endothelial permeability in capillary malformations.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cerebrospinal fluid proteomics for predictive assessment of Alzheimer's Disease risk.medRxiv : the preprint server for health sciences · 2025Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Breakdown of the neurovascular unit is associated with blood-brain barrier (BBB) leakiness contributing to cognitive decline and disease pathology in the early stages of Alzheimer's disease (AD). Vascular stability depends on angiopoietin-1 (ANGPT-1) signalling, antagonised by angiopoietin-2 (ANGPT-2) expressed upon endothelial injury. We examined the relationship between CSF ANGPT-2 and CSF markers of BBB leakiness and core AD biomarkers across three independent cohorts: (i) 31 AD patients and 33 healthy controls grouped according to their biomarker profile (i.e., AD cases t-tau > 400 pg/mL, p-tau > 60 pg/mL and Aβ42 < 550 pg/mL); (ii) 121 participants in the Wisconsin Registry for Alzheimer's Prevention or Wisconsin Alzheimer's Disease Research study (84 participants cognitively unimpaired (CU) enriched for a parental history of AD, 20 participants with mild cognitive impairment (MCI), and 17 with AD); (iii) a neurologically normal cohort aged 23-78 years with paired CSF and serum samples. CSF ANGPT-2, sPDGFRβ, albumin and fibrinogen levels were measured by sandwich ELISA. In cohort (i), CSF ANGPT-2 was elevated in AD and correlated with CSF t-tau and p-tau181 but not Aβ42. ANGPT-2 also correlated positively with CSF sPDGFRβ and fibrinogen - markers of pericyte injury and BBB leakiness. In cohort (ii), CSF ANGPT-2 was highest in MCI and correlated with CSF albumin in the CU and MCI cohorts but not in AD. CSF ANGPT-2 also correlated with CSF t-tau and p-tau and with markers of neuronal injury (neurogranin and α-synuclein) and neuroinflammation (GFAP and YKL-40). In cohort (iii), CSF ANGPT-2 correlated strongly with the CSF/serum albumin ratio. Serum ANGPT-2 showed non-significant positive associations with CSF ANGPT-2 and the CSF/serum albumin ratio. Together, these data indicate that CSF and possibly serum ANGPT-2 is associated with BBB leakiness in early AD and is closely related to tau pathology and neuronal injury. The utility of serum ANGPT-2 as a biomarker of BBB damage in AD requires further study.
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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.