Neurovascular unit dysfunction in Alzheimer’s disease

Abstract

Background Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide. Histopathologically, AD presents with two hallmarks: neurofibrillary tangles (NFTs), and aggregates of amyloid β peptide (Aβ) both in the brain parenchyma as neuritic plaques, and around blood vessels as cerebral amyloid angiopathy. According to the vascular hypothesis of AD, vascular risk factors can result in dysregulation of the neurovascular unit (NVU) and hypoxia. Hypoxia may reduce Aβ clearance from the brain and increase its production, leading to both parenchymal and vascular accumulation of Aβ. An increase in Aβ amplifies neuronal dysfunction, NFT formation, and accelerates neurodegeneration, resulting in dementia. Our aim, we analyzed different Aβ species and their association with NVU. Method We evaluated controls and AD human brains. Immunofluorescence assays were performed against different Aβ species and the main cellular and structural components of the NVU. Result Our results evidenced that there are insoluble vascular deposits of both full-length and truncated Aβ species. Furthermore, insoluble vascular Aβ aggregates are associated with a decrease phenotype of the cellular components that make up the NVU, as well as with the BBB disruption. Conclusion This new insight into the pathological role of insoluble vascular Aβ could help to identify new therapeutic targets against key molecules and receptors in NVU, which may prevent or treat the insoluble Aβ vascular accumulation in AD brains.