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 immuno fluorescence 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 language | English |
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Article number | 3654 |
Number of pages | 18 |
Journal | International Journal of Molecular Sciences |
Volume | 22 |
Issue number | 7 |
DOIs | |
Publication status | Published - 1 Apr 2021 |
Bibliographical note
Funding: This work was supported by Fondo Nacional de Ciencia y Tecnologia, FONDOCyT, from the Ministry of Higher Education, Science and Technology, Dominican Republic (2015-3A2-127 to MP-H) and (2018-2019-2A3-208 to J.L.-M. and M.P.-H).Acknowledgments: The authors want to express their gratitude to the following: P. Davies†(Albert Einstein College of Medicine, Bronx, NY, USA) and Lester I. Binder† (North Western, Chicago, IL,
USA) for the generous gift of mAbs TG-3 and Alz-50, and Tau-1, Tau-5, and Tau-7, respectively; Tec. Amparo Viramontes Pintos for the handling of the brain tissue; support in the confocal microscopy
unit of CIIDIR Durango, Instituto Politécnico Nacional; Union Medica University Clinic, Dominican
Republic, for their support and collaboration in the development of this research project. We also want to express our gratitude to the Mexican families who have donated the brain of their loved
ones affected by Alzheimer’s disease and made our research possible. This work is dedicated to the memory of José Raúl Mena López†
.
†Deceased.
Keywords
- Alzheimer’s disease
- fibrillar amyloid
- pyroglutamate-modified amyloid-beta peptides
- neurovascular unit
- blood–brain barrier
- caspase-5
- Caspase-5
- Neurovascular unit
- Fibrillar amyloid
- Pyroglutamate-modified amyloid-beta peptides
- Blood–brain barrier