Insoluble Vascular Amyloid Deposits Trigger Disruption of the Neurovascular Unit in Alzheimer's Disease Brains

Alzheimer's disease (AD) is a neurodegenerative disease, characterized histopathologically by intra-neuronal tau-related lesions and by the accumulation of amyloid beta-peptide (A beta) 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 A beta vascular accumulation and promote neuronal dysfunction, accelerating neurodegeneration and dementia. To date, the effects of insoluble vascular A beta deposits on the NVU and the blood-brain barrier (BBB) are unknown. In this study, we analyze different A beta 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 A beta and the main elements that constitute the NVU. Our results showed that there are insoluble vascular deposits of both full-length and truncated A beta 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 A beta in AD.

Automated summary

Alzheimer's disease is a neurodegenerative disease characterized by Aβ vascular accumulation, leading to neuronal dysfunction and accelerated neurodegeneration. The study found insoluble Aβ vascular deposits in the brains of AD patients, associated with a decrease in cellular components of the NVU and BBB disruption. This approach could help identify new therapeutic targets against key molecules in the NVU to prevent the accumulation of vascular fibrillar Aβ in AD.