The neuroimmune axis of Alzheimer’s disease

Genome Medicine, Journal Year: 2023, Volume and Issue: 15(1)

Published: Jan. 26, 2023

Abstract Alzheimer’s disease (AD) is a genetically complex and heterogeneous disorder with multifaceted neuropathological features, including β-amyloid plaques, neurofibrillary tangles, neuroinflammation. Over the past decade, emerging evidence has implicated both beneficial pathological roles for innate immune genes cells, peripheral cells such as T which can infiltrate brain either ameliorate or exacerbate AD neuropathogenesis. These findings support neuroimmune axis of AD, in interplay adaptive systems inside outside critically impacts etiology pathogenesis AD. In this review, we discuss complexities neuropathology at levels genetics cellular physiology, highlighting signaling pathways associated risk interactions among brain. We emphasize role mechanisms by monocytes, influence neuropathology, microglial clearance amyloid-β peptide, key component plaque cores, pro-inflammatory cytotoxic activity microglia, astrogliosis, their vasculature. Finally, review challenges outlook establishing immune-based therapies treating preventing

Language: Английский

---

The Glymphatic System in Humans: Investigations With Magnetic Resonance Imaging

Investigative Radiology, Journal Year: 2023, Volume and Issue: 59(1), P. 1 - 12

Published: March 10, 2023

Abstract The concept of the glymphatic system was proposed more than a decade ago as mechanism for interstitial fluid flow and waste removal in central nervous system. function has been shown to be particularly activated during sleep. Dysfunction implicated several neurodegenerative diseases. Noninvasive vivo imaging is expected useful elucidating pathophysiology these Currently, magnetic resonance most commonly used technique evaluate humans, large number studies have reported. This review provides comprehensive overview investigations human using imaging. can divided into 3 categories, including without gadolinium-based contrast agents (GBCAs), with intrathecal administration GBCAs, intravenous GBCAs. purpose examine not only movement brain parenchyma, but also dynamics perivascular subarachnoid spaces, well parasagittal dura meningeal lymphatics. Recent research even extended include eye inner ear. serves an important update guide future directions.

Language: Английский

---

Functional analysis of the human perivascular subarachnoid space

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 5, 2024

Abstract The human subarachnoid space harbors the cerebrospinal fluid, which flows within a landscape of blood vessels and trabeculae. Functional implications anatomy remain far less understood. This study 75 patients utilizes fluid tracer (gadobutrol) consecutive magnetic resonance imaging to investigate features early (i.e. 2-3 h after injection) propagation space. There is time-dependent perivascular pattern enrichment antegrade along major cerebral artery trunks; anterior-, middle-, posterior arteries. correlation between time first around arteries in nearby cortex significant. These observations suggest existence compartmentalized space, where ensheathment facilitates passage towards brain tissue. Periarterial transport impaired subjects with reduced intracranial pressure-volume reserve capacity idiopathic normal pressure hydrocephalus who also show increased size.

Language: Английский

---

Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

---

Roles of Cytokines in Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5803 - 5803

Published: May 26, 2024

The neuroimmune system is a collection of immune cells, cytokines, and the glymphatic that plays pivotal role in pathogenesis progression Alzheimer’s disease (AD). Of particular focus are group signaling molecules facilitate communication among cells contribute to inflammation AD. Extensive research has shown dysregulated secretion certain cytokines (IL-1β, IL-17, IL-12, IL-23, IL-6, TNF-α) promotes neuroinflammation exacerbates neuronal damage However, anti-inflammatory (IL-2, IL-3, IL-33, IL-35) also secreted during AD onset progression, thereby preventing neuroinflammation. This review summarizes involvement pro- pathology discusses their therapeutic potential.

Language: Английский

---

Current Understanding of the Anatomy, Physiology, and Magnetic Resonance Imaging of Neurofluids: Update From the 2022 “ISMRM Imaging Neurofluids Study group” Workshop in Rome

Journal of Magnetic Resonance Imaging, Journal Year: 2023, Volume and Issue: 59(2), P. 431 - 449

Published: May 4, 2023

Neurofluids is a term introduced to define all fluids in the brain and spine such as blood, cerebrospinal fluid, interstitial fluid. Neuroscientists past millennium have steadily identified several different fluid environments that interact synchronized harmonious manner assure healthy microenvironment required for optimal neuroglial function. Neuroanatomists biochemists provided an incredible wealth of evidence revealing anatomy perivascular spaces, meninges glia their role drainage neuronal waste products. Human studies been limited due restricted availability noninvasive imaging modalities can provide high spatiotemporal depiction neurofluids. Therefore, animal key advancing our knowledge temporal spatial dynamics fluids, example, by injecting tracers with molecular weights. Such sparked interest identify possible disruptions neurofluids human diseases small vessel disease, cerebral amyloid angiopathy, dementia. However, differences between rodent physiology should be considered when extrapolating these findings understand brain. An increasing armamentarium MRI techniques being built markers altered pathways. During three‐day workshop organized International Society Magnetic Resonance Medicine was held Rome September 2022, concepts were discussed distinguished international faculty lay basis what known where we still lack evidence. We envision next decade, will allow neurofluid pathways true pathological processes underlying disease discover new avenues early diagnoses treatments including drug delivery. Evidence level: 1 Technical Efficacy: Stage 3

Language: Английский

---

Glymphatic dysfunction in patients with early-stage amyotrophic lateral sclerosis

Brain, Journal Year: 2023, Volume and Issue: 147(1), P. 100 - 108

Published: Aug. 16, 2023

Abstract Recently, an astrocytic aquaporin 4-dependent drainage system, that is, the glymphatic has been identified in live murine and human brain. Growing evidence suggests function is impaired patients with several neurodegenerative diseases, including Alzheimer’s Parkinson’s disease. As third most common disease, although animal studies have indicated early dysfunction likely important pathological mechanism underpinning amyotrophic lateral sclerosis (ALS), no available study conducted to thoroughly assess vivo ALS date, particularly early-stage ALS. Thus, using diffusion tensor imaging analysis along perivascular space (ALPS) index, approximate measure of vivo, we aimed explore whether ALS, diagnostic performance ALPS index distinguishing between healthy subjects. We also identify relationships clinical disabilities sleep problems In this retrospective study, King’s Stage 1 were defined as enrolled 56 32 age- sex-matched control All participants completed screening, assessment analysis. For assessment, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale polysomnography used. Compared subjects, had a significantly lower after family-wise error correction (P < 0.05). Moreover, receiver operating characteristic showed area under curve for was 0.792 (95% confidence interval 0.700–0.884). Partial correlation analyses correlated disability disturbances Multivariate efficiency (r = 0.419, P 0.002) periodic limb movements −0.294, 0.017) significant predictive factors conclusion, our continues support role pathology, provide additional insights into value its suggest improvement may be promising strategy slowing process Future are needed therapeutic individuals presymptomatic-stage diseases.

Language: Английский

---

Human brain solute transport quantified by glymphatic MRI-informed biophysics during sleep and sleep deprivation

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

Published: Aug. 18, 2023

Whether you are reading, running or sleeping, your brain and its fluid environment continuously interacts to distribute nutrients clear metabolic waste. Yet, the precise mechanisms for solute transport within human have remained hard quantify using imaging techniques alone. From multi-modal MRI data sets in sleeping sleep-deprived subjects, we identify CSF tracer parameters forward inverse subject-specific computational modelling. Our findings support notion that extracellular diffusion alone is not sufficient as a brain-wide mechanism. Instead, show observations align well with by either an effective coefficent 3.5[Formula: see text] of combination local clearance rates corresponding half-life up 5 h, augmented advection average flow speeds on order 1-9 [Formula: text]m/min. Reduced fully explains reduced after sleep-deprivation, supporting role sleep deprivation clearance.

Language: Английский

---

Glymphatic system: an emerging therapeutic approach for neurological disorders

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: July 6, 2023

The functions of the glymphatic system include clearance metabolic waste and modulation water transport in brain, it forms a brain-wide fluid network along with cerebrospinal (CSF) interstitial (ISF). pathway consists periarterial influx CSF, astrocyte-mediated interchange between ISF CSF supported by aquaporin-4 (AQP4) on endfeet astrocyte around periarterioles, perivenous efflux CSF. Finally, is absorbed arachnoid granules or flows into cervical lymphatic vessels. There growing evidence from animal experiments that dysfunction involved many neurological disorders, such as Alzheimer’s disease, stroke, epilepsy, traumatic brain injury meningitis. In this review, we summarize latest progress its driving factors, well changes different diseases. We significantly highlight likely therapeutic approaches for diseases, importance AQP4 normal sleep architecture process.

Language: Английский

---

Delivery of gene therapy through a cerebrospinal fluid conduit to rescue hearing in adult mice

Science Translational Medicine, Journal Year: 2023, Volume and Issue: 15(702)

Published: June 28, 2023

Inner ear gene therapy has recently effectively restored hearing in neonatal mice, but it is complicated adulthood by the structural inaccessibility of cochlea, which embedded within temporal bone. Alternative delivery routes may advance auditory research and also prove useful when translated to humans with progressive genetic-mediated loss. Cerebrospinal fluid flow via glymphatic system emerging as a new approach for brain-wide drug rodents well humans. The cerebrospinal inner are connected bony channel called cochlear aqueduct, previous studies have not explored possibility delivering restore adult deaf mice. Here, we showed that aqueduct mice exhibits lymphatic-like characteristics. In vivo time-lapse magnetic resonance imaging, computed tomography, optical fluorescence microscopy large-particle tracers injected into reached dispersive transport A single intracisternal injection adeno-associated virus carrying solute carrier family 17, member 8 ( Slc17A8 ), encodes vesicular glutamate transporter-3 (VGLUT3), rescued −/− restoring VGLUT3 protein expression hair cells, minimal ectopic brain none liver. Our findings demonstrate comprises an accessible route represent important step toward using

Language: Английский

---