ArticleBrain pathology (Zurich, Switzerland)2021
Mediators of cerebral hypoperfusion and blood-brain barrier leakiness in Alzheimer's disease, vascular dementia and mixed dementia.
Article in Brain pathology (Zurich, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- A systematic review and meta-analysis on the transcriptomic signatures in alcohol use disorder.Molecular psychiatry · 2025Pooled it
- "Morphological, Functional, and Molecular Progression of Blood-Brain Barrier Dysfunction in Alzheimer's Disease".Journal of molecular neuroscience : MN · 2026Review
- New perspectives on VEGF signalling in Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2026Review
- Metabolic Syndrome and Dementia Risk in Older Adults: A Narrative Review.The Kaohsiung journal of medical sciences · 2026Review
- Systematic Design and Evaluation of Nasal Drug Delivery for Central Nervous System Disease from Experimental to Clinical Application.Pharmaceutics · 2026Review
- Therapeutic targeting of neuroimmune mechanisms in neurodegeneration.Nature reviews. Drug discovery · 2026Review
- Blood-Brain Barrier Permeability in Cases of Post-operative Delirium Is Associated with Central Nervous System Phosphatidylcholine Imbalances.Molecular neurobiology · 2026Article
- Post-mortem evidence of pathogenic angiogenesis and abnormal vascular function in early Alzheimer's disease.Brain : a journal of neurology · 2026Article
- Morin Improves Cognitive Deficits in an in Vivo Model of Vascular Dementia by Modulating the N-methyl-D-aspartate Receptor Signaling Pathways.Neurochemical research · 2026Article
- Evaluating Basigin as a Potential Biomarker of Blood-Brain Barrier Dysfunction in Cerebral Amyloid Angiopathy.Neuropathology and applied neurobiology · 2026Article
- 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
- Alzheimer's disease PSEN-2 N141I mutation reveals altered and shear-sensitive brain endothelial cell-like phenotype in human iPSC-derived models.Acta neuropathologica communications · 2025Article
- Single nucleus RNA sequencing unveils relationship between microglia and endothelial cells in mixed Alzheimer's disease and vascular pathology.Neurobiology of disease · 2025Article
- Restoring brain barriers: an innovative approach for treating neurological disorders.Fluids and barriers of the CNS · 2025Review
- Stroke Exacerbates Respiratory Disorder and Cognition Impairment in Mice with Cerebral Amyloid Angiopathy.Aging and disease · 2025Article
- Interplay Between Vascular Dysfunction and Neurodegenerative Pathology: New Insights into Molecular Mechanisms and Management.Biomolecules · 2025Review
- The intersection of delirium and long-term cognition in older adults: the critical role of delirium prevention.Journal of neurology · 2025Review
- Blood-Brain Barrier (BBB) Dysfunction in CNS Diseases: Paying Attention to Pericytes.CNS neuroscience & therapeutics · 2025Review
- Hypotension with neurovascular changes and cognitive dysfunction: An epidemiological, pathobiological, and treatment review.Chinese medical journal · 2025Review
- Exercise-mediated cerebrovascular repair in Alzheimer's disease: from pathophysiology to therapeutic precision.Frontiers in aging neuroscience · 2025Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
In vascular dementia (VaD) and Alzheimer's disease (AD), cerebral hypoperfusion and blood-brain barrier (BBB) leakiness contribute to brain damage. In this study, we have measured biochemical markers and mediators of cerebral hypoperfusion and BBB in the frontal (BA6) and parietal (BA7) cortex and underlying white matter, to investigate the pathophysiology of vascular dysfunction in AD, VaD and mixed dementia. The ratio of myelin-associated glycoprotein to proteolipid protein-1 (MAG:PLP1), a post-mortem biochemical indicator of the adequacy of ante-mortem cerebral perfusion; the concentration of fibrinogen adjusted for haemoglobin level, a marker of blood-brain barrier (BBB) leakiness; the level of vascular endothelial growth factor-A (VEGF), a marker of tissue hypoxia; and endothelin-1 (EDN1), a potent vasoconstrictor, were measured by ELISA in the frontal and parietal cortex and underlying white matter in 94 AD, 20 VaD, 33 mixed dementia cases and 58 age-matched controls. All cases were assessed neuropathologically for small vessel disease (SVD), cerebral amyloid angiopathy (CAA) severity, Aβ and phospho-tau parenchymal load, and Braak tangle stage. Aβ40 and Aβ42 were measured by ELISA in guanidine-HCl tissue extracts. We found biochemical evidence of cerebral hypoperfusion in AD, VaD and mixed dementia to be associated with SVD, Aβ level, plaque load, EDN1 level and Braak tangle stage, and to be most widespread in mixed dementia. There was evidence of BBB leakiness in AD-limited to the cerebral cortex and related to EDN1 level. In conclusion, abnormalities of cerebral perfusion and BBB function in common types of dementia can largely be explained by a combination of arteriolosclerosis, and Aβ-, tau- and endothelin-related vascular dysfunction. The relative contributions of these processes vary considerably both between and within the diseases.
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