Cell-specific transcriptional signatures of vascular cells in Alzheimer’s disease: perspectives, pathways, and therapeutic directions DOI Creative Commons
Soumilee Chaudhuri, Minyoung Cho,

Julia C. Stumpff

et al.

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 29, 2025

Abstract Alzheimer’s disease (AD) is a debilitating neurodegenerative that marked by profound neurovascular dysfunction and significant cell-specific alterations in the brain vasculature. Recent advances high throughput single-cell transcriptomics technology have enabled study of human vasculature at an unprecedented depth. Additionally, understudied niche cerebrovascular cells, such as endothelial mural their subtypes been scrutinized for understanding cellular transcriptional heterogeneity AD. Here, we provide overview rich signatures derived from recent single-nucleus transcriptomic studies vascular cells implications targeted therapy We conducted in-depth literature search using Medline Covidence to identify pertinent AD utilized technologies post-mortem tissue focusing on differences cell types cognitively normal older adults. also discuss impaired crosstalk between neuroglial units, well astrocytes contextualize findings distinct smooth muscle fibroblasts, pericytes highlight pathways potential therapeutic interventions concerted multi-omic effort with spatial technology, neuroimaging, neuropathology. Overall, detailed account crucial unit. Graphical Endothelial mediate dysregulated cell-cell interactions The unit (NVU) composed various types, including (pericytes, cells), fibroblast neurons, microglia, astrocytes. Dysregulated involve multiple pathways, notably immune responses, angiogenesis common both cells. involving neuroinflammation amyloid clearance are prominent while exhibit related growth factors, cytoskeletal remodeling synaptic function. In addition, within NVU gliovascular (GVU) altered AD, communication evident, increased pericytes, decreased astrocytes, neurons. Figure created BioRender.com. Abbreviations: Alzheimer's disease; NVU, Neurovascular unit; CNS, Central Nervous System.

Language: Английский

Aquaporin-4 and Parkinson’s Disease DOI Open Access
К. В. Лапшина, И. В. Екимова

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1672 - 1672

Published: Jan. 30, 2024

The water-selective channel aquaporin-4 (AQP4) is implicated in water homeostasis and the functioning of glymphatic system, which eliminates various metabolites from brain tissue, including amyloidogenic proteins. Misfolding α-synuclein protein its post-translational modifications play a crucial role development Parkinson’s disease (PD) other synucleopathies, leading to formation cytotoxic oligomers aggregates that cause neurodegeneration. Human animal studies have shown an interconnection between AQP4 dysfunction accumulation; however, specific these mechanisms remains unclear. This review summarizes current knowledge on progression pathology, considering possible effects dysregulation molecular can impact modification, accumulation aggregation. It also highlights future directions help study protective during PD neurodegenerative diseases.

Language: Английский

Citations

9
Near-Infrared Imaging of Glymphatic Clearance in a Pre-Clinical Model of Repetitive Closed Head Traumatic Brain Injury DOI Creative Commons
Eleftheria Michalaki, Alexis N. Pulliam,

Pooja M. Datta Roy

et al.

Neurotrauma Reports, Journal Year: 2025, Volume and Issue: 6(1), P. 115 - 128

Published: Jan. 1, 2025

Traumatic brain injury (TBI) is a major health disorder for which there are few treatments. The glymphatic system the brain's inbuilt lymphatic-like that thought to be responsible clearing waste products from lymph nodes. Although evidence drainage crucial homeostasis, its role in TBI pathogenesis remains elusive. Here, we investigated how clearance altered following rats using real-time non-invasive imaging. Twenty-four hours repetitive closed-head or sham conditions, injected infrared dye intraventricularly and used near-infrared (NIR) imaging quantify signal intensity, intensity over time, appearance time of NIR different regions. yielded lower rate change lateral ventricle surrounding parietal cortex compared with indicating reduced cerebrospinal fluid perfusion. took significantly longer reach anterior regions brain, while perfusion posterior was faster animals. Aquaporin-4 (AQP4) expression 24 h after across all cortical examined ventral at coronal levels, suggesting complex relationship between AQP4 glymph function. Furthermore, revealed detectable cervical nodes (CLNs) animals but not animals, yet blood accumulation CLNs TBI-related extravascular removed through system. These data indicate disrupts normal efflux kinetics reduces CLNs, demonstrating restoring function may promising therapeutic target.

Language: Английский

Citations

1
Brain vasculature accumulates tau and is spatially related to tau tangle pathology in Alzheimer’s disease DOI Creative Commons
Zachary Hoglund, Nancy E. Ruiz‐Uribe, Eric del Sastre

et al.

Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 147(1)

Published: June 1, 2024

Insoluble pathogenic proteins accumulate along blood vessels in conditions of cerebral amyloid angiopathy (CAA), exerting a toxic effect on vascular cells and impacting homeostasis. In this work, we provide new evidence from three-dimensional human brain histology that tau protein, the main component neurofibrillary tangles, can similarly segments. We quantitatively assessed n = 6 Alzheimer's disease (AD), normal aging control brains saw tau-positive vessel segments were present all AD cases. Tau-positive are enriched for at levels higher than surrounding tissue appear to affect arterioles across cortical layers (I-V). Further, isolated these tissues N-terminal phosphorylated T181 T217. Importantly, associated with local areas increased tangles. This suggests accumulation around may reflect clearance failure. sum, data indicate tau, like beta, accumulates exert significant influence vasculature setting AD.

Language: Английский

Citations

8
Astrocyte aquaporin mediates a tonic water efflux maintaining brain homeostasis DOI Creative Commons
Cuong Pham, Yuji Komaki, Anna Deàs-Just

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: April 11, 2024

Brain water homeostasis not only provides a physical protection, but also determines the diffusion of chemical molecules key for information processing and metabolic stability. As major type glia in brain parenchyma, astrocytes are dominant cell expressing aquaporin channel. How astrocyte contributes to basal physiology remains be understood. We report that 4 (AQP4) mediates tonic efflux conditions. Acute inhibition AQP4 leads intracellular accumulation as optically resolved by fluorescence-translated imaging acute slices, vivo fiber photometry mobile mice. then show aquaporin-mediated constant maintains volume osmotic equilibrium, neuron Ca2+ signaling, extracellular space remodeling during optogenetically induced cortical spreading depression. Using diffusion-weighted magnetic resonance (DW-MRI), we observed heterogeneously disturbs region-dependent manner. Our data suggest aquaporin, though bidirectional nature, outflow sustain cellular environmental equilibrium parenchyma.

Language: Английский

Citations

7
Association of Extent of Transverse Sinus Stenosis With Cerebral Glymphatic Clearance in Patients With Idiopathic Intracranial Hypertension DOI

Derrek Schartz,

Alan Finkelstein, Matthew T. Bender

et al.

Neurology, Journal Year: 2024, Volume and Issue: 103(1)

Published: June 4, 2024

Idiopathic intracranial hypertension (IIH) is a neurologic disorder characterized by symptoms of elevated pressure in the absence clear cause. There developing theory that IIH may, part, be related to abnormal cerebral glymphatic clearance. In addition, transverse sinus stenosis (TSS) common finding unclear pathophysiologic significance. Similarly, whether or not TSS associated with outflow unknown. The aim this investigation was explore possible association between and extent patients IIH.

Language: Английский

Citations

7
Structural characterization of SLYM—a 4th meningeal membrane DOI Creative Commons
Virginia Plá,

Styliani Bitsika,

Michael Giannetto

et al.

Fluids and Barriers of the CNS, Journal Year: 2023, Volume and Issue: 20(1)

Published: Dec. 14, 2023

Abstract Traditionally, the meninges are described as 3 distinct layers, dura, arachnoid and pia. Yet, classification of connective meningeal membranes surrounding brain is based on postmortem macroscopic examination. Ultrastructural single cell transcriptome analyses have documented that layers can be subdivided into several cellular characteristics. We here re-examined existence a 4 th membrane, Subarachnoid Lymphatic-like Membrane or SLYM in Prox1-eGFP reporter mice. Imaging freshly resected whole brains showed covers entire stem forms roof shielding subarachnoid cerebrospinal fluid (CSF)-filled cisterns pia-adjacent vasculature. Thus, strategically positioned to facilitate periarterial influx produced CSF thereby support unidirectional glymphatic transport. Histological analysis that, spinal cord parts dorsal cortex, fused with barrier layer, while basal typically formed 1–3 layered membrane subdividing space two compartments. However, great care should taken when interpreting organization delicate leptomeningeal tissue sections. show hyperosmotic fixatives dehydrate risk shrinkage dislocation these fragile preparations.

Language: Английский

Citations

15
Astrocytic crosstalk with brain and immune cells in healthy and diseased conditions DOI Creative Commons

Se Young Lee,

Won‐Suk Chung

Current Opinion in Neurobiology, Journal Year: 2024, Volume and Issue: 84, P. 102840 - 102840

Published: Jan. 29, 2024

Astrocytes interact with various cell types, including neurons, vascular cells, microglia, and peripheral immune cells. These interactions are crucial for regulating normal brain functions as well modulating neuroinflammation in pathological conditions. Recent transcriptomic proteomic studies have identified critical molecules involved astrocytic crosstalk other shedding light on their roles maintaining homeostasis both healthy diseased perform these through either direct or indirect physical associations neuronal synapses vasculature. Furthermore, astrocytes can communicate such T natural killer secreted during neuroinflammation. In this review, we discuss the molecular basis of underlying mechanisms astrocyte communication We propose that function a central hub inter-connecting vasculatures, cells brains.

Language: Английский

Citations

5
Multifaceted Roles of Aquaporins in the Pathogenesis of Alzheimer’s Disease DOI Open Access
Kaoru Yamada

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6528 - 6528

Published: March 31, 2023

The central nervous system is highly dependent on water, and disturbances in water homeostasis can have a significant impact its normal functions. regulation of balance is, at least part, carried out via specialized channels called aquaporins. In the system, two major aquaporins (AQPs), AQP1 AQP4, their potential involvements been long implicated pathophysiology many brain disorders such as edema Neuromyelitis optica. addition to these diseases, there growing attention involvement AQPs removal waste products Alzheimer's disease (AD). This indicates that targeting fluid novel attractive approach for AD. review article aims summarize recent knowledge pathological implications AD, discussing unsolved questions future prospects.

Language: Английский

Citations

13
Effects of sleep on brain perivascular space in a cognitively healthy population DOI Creative Commons
Nien‐Chu Shih, Giuseppe Barisano, Karen D. Lincoln

et al.

Sleep Medicine, Journal Year: 2023, Volume and Issue: 111, P. 170 - 179

Published: Sept. 25, 2023

The magnetic resonance imaging (MRI) visible perivascular space (PVS) reportedly clears amyloid-β and metabolic waste during sleep. Previous studies reported an association between sleep the PVS in small vessel disease, traumatic brain injury, Alzheimer's disease. However, this relationship a healthy cohort is still unclear. Here, we used Human Connectome Project Aging dataset to analyze cognitively adults across aging continuum. We measured parameters using self-reported Pittsburgh Sleep Quality Index questionnaire. found that older who had better quality efficiency presented with larger volume fraction basal ganglia (BG). measures were not associated centrum semiovale (CSO). In addition, body mass index (BMI) influenced BG-PVS middle-aged participants. entire cohort, effect of on was mediated by BMI. BMI did influence cohort. Furthermore, there are significant differences racial/ethnic cohorts. summary, alteration different adults.

Language: Английский

Citations

11
Repetitive head trauma and apoE4 induce chronic cerebrovascular alterations that impair tau elimination from the brain DOI
Maxwell Eisenbaum, Andrew Pearson, Camila Ortiz

et al.

Experimental Neurology, Journal Year: 2024, Volume and Issue: 374, P. 114702 - 114702

Published: Jan. 30, 2024

Language: Английский

Citations

4