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Abstract Disruptions in pericyte and endothelial cell communication can compromise the integrity of the blood-brain barrier (BBB), leading to neurovascular dysfunction and the development of neurological disorders. However, the evaluation of microvessel RNAs has been limited to tissue homogenates, with spatial visualization only available for protein targets. The aim of the present study is the development of an innovative microvessel isolation technique that is RNA-friendly for the purpose of coupling with in situ hybridization RNAscope analysis. RNA-friendly microvessel isolation combined with RNAscope analysis enables the visualization of cell-specific RNA within the spatial and histological context of the BBB. Using this approach, we have gained valuable insights into the structural and functional differences associated with the microvessels of 5xFAD mice, a mouse model of Alzheimer’s disease (AD). RNAscope analysis revealed a decrease in pericytes from microvessels isolated from 5xFAD mice in comparison to wild-type mice. Additionally, the microvessels of 5xFAD mice exhibited an increase in TYRO protein tyrosine kinase binding protein (TYROBP) mRNA expression. These findings significantly advance our understanding of neurovascular interactions and hold great promise for guiding the development of targeted therapeutic interventions. This innovative approach enables visualization of cell RNA while preserving the spatial and histological context of the BBB, shedding light on the mechanisms underlying neurovascular unit communication.

Abstract While HIV-1 is primarily an infection of CD4 + T cells, there is an emerging interest towards understanding how infection of other cell types can contribute to HIV-associated comorbidities. For HIV-1 to cross from the blood stream into tissues, the virus must come in direct contact with the vascular endothelium, including pericytes that envelope vascular endothelial cells. Pericytes are multifunctional cells that have been recognized for their essential role in angiogenesis, vessel maintenance, and blood flow rate. Most importantly, recent evidence has shown that pericytes can be a target of HIV-1 infection and support an active stage of the viral life cycle, with latency also suggested by in vitro data. Pericyte infection by HIV-1 has been confirmed in the postmortem human brains and in lungs from SIV-infected macaques. Moreover, pericyte dysfunction has been implicated in a variety of pathologies ranging from ischemic stroke to diabetes, which are common comorbidities among people with HIV-1. In this review, we discuss the role of pericytes during HIV-1 infection and their contribution to the progression of HIV-associated comorbidities.

Summary: For more than a century, clinicians have been aware of the devastating neurological condition called Alzheimer’s disease (AD). AD is characterized by the presence of abnormal amyloid protein plaques and tau tangles in the brain. The dominant hypothesis, termed the amyloid hypothesis, attributes AD development to excessive cleavage and accumulation of amyloid precursor protein (APP), leading to brain tissue atrophy. The amyloid hypothesis has greatly influenced AD research and therapeutic endeavors. However, despite significant attention, a complete understanding of amyloid and APP’s roles in disease pathology, progression, and cognitive impairment remains elusive. Recent controversies and several unsuccessful drug trials have called into question whether amyloid is the only neuropathological factor for treatment. To accomplish disease amelioration, we argue that researchers and clinicians may need to take a compounding approach to target amyloid and other factors in the brain, including traditional pharmaceuticals and holistic therapies.