Abstract
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 (CAA). 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. In recent decades, therapeutic approaches have attempted to decrease the levels of abnormal Aβ or tau levels in the AD brain. However, several of these approaches have either been associated with an inappropriate immune response triggering inflammation, or have failed to improve cognition. Here, we review the pathogenesis and potential therapeutic targets associated with dysfunction of the NVU in AD.
Highlights
The neurovascular unit (NVU) is defined as a complex functional and anatomical structure composed of: (a) neurons and interneurons, (b) glial cells such as microglia, astrocytes, and oligodendrocytes, (c) vascular cells such as endothelial cells, pericytes, and smooth muscle cells (SMCs), and (d) a basal lamina formed by brain endothelial cells and extracellular matrix (Figure 1) [1,2]
We review the relationship between the NVU and Blood-Brain Barrier (BBB) dysregulation and Alzheimer’s disease (AD) pathology
CD36/a3b1-integrin/CD47 complex regulates filamentous amyloid β peptide (Aβ) (fAβ) interaction in microglia cells that the presence of pathological tau has been observed as puncta in perivascular spaces in sporadic AD brains [53]
Summary
The neurovascular unit (NVU) is defined as a complex functional and anatomical structure composed of: (a) neurons and interneurons, (b) glial cells such as microglia, astrocytes, and oligodendrocytes, (c) vascular cells such as endothelial cells, pericytes, and smooth muscle cells (SMCs), and (d) a basal lamina formed by brain endothelial cells and extracellular matrix (Figure 1) [1,2]. Pial arteries (panel (b)) run along the brain surface and depict the different levels of the vascular tree. The second hallmark is the presence gether withβ-peptide astrocytic(Aβ) end-feet, pericytes, microglia, the BBB the circulating of amyloid deposits in theand brain parenchyma andseparates around cerebral blood blood components from neurons [2,33]
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