Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disease that is the most common cause of dementia, especially among aging populations. Despite advances in AD research, the underlying cause and the discovery of disease-modifying treatments have remained elusive. Two key features of AD pathology are the aberrant deposition of amyloid beta (amyloid-β or Aβ) proteins in the brain parenchyma and Aβ toxicity in brain pericytes of the neurovascular unit/blood–brain barrier (NVU/BBB). This toxicity induces oxidative stress in pericytes and leads to capillary constriction. The interaction between pericytes and Aβ proteins results in the release of endothelin-1 in the pericytes. Endothelin-1 interacts with ETA receptors to cause pericyte contraction. This pericyte-mediated constriction of brain capillaries can cause chronic hypoperfusion of the brain microvasculature, subsequently leading to the neurodegeneration and cognitive decline observed in AD patients. The interaction between Aβ proteins and brain pericytes is largely unknown and requires further investigation. This review provides an updated overview of the interaction between Aβ proteins with pericytes, one the most significant and often forgotten cellular components of the BBB and the inner blood–retinal barrier (IBRB). The IBRB has been shown to be a window into the central nervous system (CNS) that could allow the early diagnosis of AD pathology in the brain and the BBB using modern photonic imaging systems such as optical coherence tomography (OCT) and two-photon microscopy. In this review, I explore the regulation of Aβ proteins in the brain parenchyma, their role in AD pathobiology, and their association with pericyte function. This review discusses Aβ proteins and pericytes in the ocular compartment of AD patients as well as strategies to rescue or protect pericytes from the effects of Aβ proteins, or to replace them with healthy cells.
Highlights
Alzheimer’s disease (AD) is a pervasive and progressive neurodegenerative disorder that is expected to affect 14 million people in the US by 2050, with increasing incidence in aging populations
The dysregulation or loss of pericyte function can result in microvascular instability and pathological consequences
Pericyte loss due to Aβ toxicity may be an early event in AD progression, as pericyte loss reduces cerebral blood flow (CBF) and creates hypoxic areas throughout the brain
Summary
Alzheimer’s disease (AD) is a pervasive and progressive neurodegenerative disorder that is expected to affect 14 million people in the US by 2050, with increasing incidence in aging populations. AD pathology has largely been attributed to the progressive accumulation of extracellular amyloid-β (Aβ) proteins in the brain parenchyma, subsequently resulting in the formation of senile plaques and neurofibrillary tangles composed of hyperphosphorylated tau proteins [3,4] These plaques occur in vessels, causing cerebral amyloid angiopathy [4,5,6,7]. The understanding of functional changes in brain pericytes in AD patients and the mechanisms associated with AD pathobiology may lead to strategies for protecting and/or preserving pericyte function These strategies could serve as early intervention and/or treatment options that may delay, prevent, or limit AD progression. These options may be applicable to other conditions that affect the BBB such as multiple sclerosis, strokes, and various neurological tumors including glioblastoma multiforme
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