Abstract
Neurodegenerative and cerebrovascular diseases cause considerable human suffering, and therapy options for these two disease categories are limited or non‐existing. It is an emerging notion that neurodegenerative and cerebrovascular diseases are linked in several ways, and in this review, we discuss the current status regarding vascular dysregulation in neurodegenerative disease, and conversely, how cerebrovascular diseases are associated with central nervous system (CNS) degeneration and dysfunction. The emerging links between neurodegenerative and cerebrovascular diseases are reviewed with a particular focus on pericytes—important cells that ensheath the endothelium in the microvasculature and which are pivotal for blood–brain barrier function and cerebral blood flow. Finally, we address how novel molecular and cellular insights into pericytes and other vascular cell types may open new avenues for diagnosis and therapy development for these important diseases.
Highlights
The brain and its vasculature The human central nervous system (CNS) is composed of 100 billion neurons connected in intricate ways
Cell type-specific modulation of genes in genetic mouse models is increasingly used to address these issues. This field is still at an early stage, but progress in genome-editing techniques combined with improved opportunities for tissue-specific expression of CRE recombinase and specific genes facilitates advancement in making more precise mouse models, and below we provide some examples of progress in the area of genetically modified mice
Progress is made in identifying pathomechanisms for these disease categories, it is an emerging notion that there are several links between neurodegenerative and cerebrovascular diseases, and to understand these links may provide new angles for therapy development and for a more complete understanding of the disease process
Summary
The brain and its vasculature The human central nervous system (CNS) is composed of 100 billion neurons connected in intricate ways. The complex role of pericytes at the BBB is underscored by studies of mice with reduced pericyte numbers, such as the abovementioned Pdgfbret/ret mice, which eventually develop a seemingly stable pericyte-deficient brain vasculature with specific attenuation of the endothelial transcytosis barrier [20]. Single-cell RNA-sequencing (scRNA-seq) was used to provide transcriptional profiles for pericytes and all other brain vascular cell types, as well as for astrocytes and microglia [17].
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