Insoluble vascular amyloid deposits trigger disruption of the neurovascular unit in Alzheimer’s disease brains

Luis O. Soto-Rojas, B. Berenice Campa-Córdoba, Charles R. Harrington, Andrés Salas-Casas, Mario Hernandes-Alejandro, Ignacio Villanueva-Fierro, Marely Bravo-Muñoz, Linda Garcés-Ramírez, Fidel De La Cruz-López, Miguel Ángel Ontiveros-Torres, Goar Gevorkian, Mar Pacheco-Herrero, José Luna-Muñoz

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number3654
JournalInternational Journal of Molecular Sciences
Volume22
Issue number7
DOIs
StatePublished - 1 Apr 2021

Keywords

  • Alzheimer’s disease
  • Blood–brain barrier
  • Caspase-5
  • Fibrillar amyloid
  • Neurovascular unit
  • Pyroglutamate-modified amyloid-beta peptides

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