TY - JOUR
T1 - Insoluble vascular amyloid deposits trigger disruption of the neurovascular unit in Alzheimer’s disease brains
AU - Soto-Rojas, Luis O.
AU - Campa-Córdoba, B. Berenice
AU - Harrington, Charles R.
AU - Salas-Casas, Andrés
AU - Hernandes-Alejandro, Mario
AU - Villanueva-Fierro, Ignacio
AU - Bravo-Muñoz, Marely
AU - Garcés-Ramírez, Linda
AU - De La Cruz-López, Fidel
AU - Ontiveros-Torres, Miguel Ángel
AU - Gevorkian, Goar
AU - Pacheco-Herrero, Mar
AU - Luna-Muñoz, José
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/4/1
Y1 - 2021/4/1
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - Blood–brain barrier
KW - Caspase-5
KW - Fibrillar amyloid
KW - Neurovascular unit
KW - Pyroglutamate-modified amyloid-beta peptides
UR - http://www.scopus.com/inward/record.url?scp=85103334888&partnerID=8YFLogxK
U2 - 10.3390/ijms22073654
DO - 10.3390/ijms22073654
M3 - Artículo
C2 - 33915754
AN - SCOPUS:85103334888
SN - 1661-6596
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 7
M1 - 3654
ER -