Insoluble Vascular Amyloid Deposits Trigger Disruption of the Neurovascular Unit in Alzheimer's Disease Brains
| Autor: | Mario Hernandes-Alejandro, Miguel Ángel Ontiveros-Torres, Mar Pacheco-Herrero, Marely Bravo-Muñoz, Fidel de la Cruz-Lopez, Andrés Salas-Casas, Luis O Soto-Rojas, B. Berenice Campa-Córdoba, Ignacio Villanueva-Fierro, Linda Garcés-Ramírez, José Luna-Muñoz, Charles R. Harrington, Goar Gevorkian |
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| Rok vydání: | 2021 |
| Předmět: |
Pathology
medicine.medical_specialty caspase-5 Amyloid blood–brain barrier Blood–brain barrier Immunofluorescence Article Catalysis Tight Junctions lcsh:Chemistry Inorganic Chemistry Alzheimer Disease Parenchyma medicine Dementia Humans neurovascular unit Physical and Theoretical Chemistry Receptor lcsh:QH301-705.5 Molecular Biology Spectroscopy Aged Aged 80 and over Amyloid beta-Peptides fibrillar amyloid medicine.diagnostic_test Chemistry Organic Chemistry Neurodegeneration Brain General Medicine medicine.disease Phenotype Actins Computer Science Applications pyroglutamate-modified amyloid-beta peptides medicine.anatomical_structure lcsh:Biology (General) lcsh:QD1-999 Astrocytes Case-Control Studies Caspases Blood Vessels Microglia Alzheimer’s disease |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 3654, p 3654 (2021) International Journal of Molecular Sciences Volume 22 Issue 7 |
| ISSN: | 1422-0067 |
| Popis: | Alzheimer’s disease (AD) is a neurodegenerative disease, characterized histopathologically by intra-neuronal tau-related lesions and by the accumulation of amyloid β-peptide (Aβ) in the brain parenchyma and around cerebral blood vessels. According to the vascular hypothesis of AD, an alteration in the neurovascular unit (NVU) could lead to Aβ vascular accumulation and promote neuronal dysfunction, accelerating neurodegeneration and dementia. To date, the effects of insoluble vascular Aβ deposits on the NVU and the blood–brain barrier (BBB) are unknown. In this study, we analyze different Aβ species and their association with the cells that make up the NVU. We evaluated post-mortem AD brain tissue. Multiple immunofluorescence assays were performed against different species of Aβ and the main elements that constitute the NVU. Our results showed that there are insoluble vascular deposits of both full-length and truncated Aβ species. Besides, insoluble aggregates are associated with a decrease in the phenotype of the cellular components that constitute the NVU and with BBB disruption. This approach could help identify new therapeutic targets against key molecules and receptors in the NVU that can prevent the accumulation of vascular fibrillar Aβ in AD. |
| Databáze: | OpenAIRE |
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