The association of microbial infection and adaptive immune cell activation in Alzheimer’s disease DOI Creative Commons
Mathew Clement

Discovery Immunology, Journal Year: 2023, Volume and Issue: 2(1)

Published: Jan. 1, 2023

Summary Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. Early symptoms include loss memory mild cognitive ability; however, as progresses, these can present with increased severity manifesting mood behaviour changes, disorientation, motor/body control. AD one leading causes death in UK, an ever-increasing ageing society, patient numbers are predicted to rise posing significant global health emergency. complex neurophysiological where pathology characterized by deposition aggregation misfolded amyloid-beta (Aβ)-protein that in-turn promotes excessive tau-protein production which together drives neuronal cell dysfunction, neuroinflammation, neurodegeneration. It widely accepted driven combination both genetic immunological processes recent data suggesting adaptive immune activity within parenchyma occurs throughout disease. The mechanisms behind observations remain unclear but suggest manipulating response during may be effective therapeutic strategy. Using immunotherapy for treatment not new concept only two approved treatments use antibody-based approaches target Aβ. However, have been shown temporarily ease or slow progression highlighting urgent need newer treatments. This review discusses role system AD, how microbial infections contributing inflammatory suggests pose targets this devastating

Language: Английский

Neurological complications caused by SARS-CoV-2 DOI
Zehan Pang, Ao Tang,

Yujie He

et al.

Clinical Microbiology Reviews, Journal Year: 2024, Volume and Issue: 37(4)

Published: Sept. 18, 2024

SUMMARYSARS-CoV-2 can not only cause respiratory symptoms but also lead to neurological complications. Research has shown that more than 30% of SARS-CoV-2 patients present neurologic during COVID-19 (A. Pezzini and A. Padovani, Nat Rev Neurol 16:636-644, 2020, https://doi.org/10.1038/s41582-020-0398-3). Increasing evidence suggests invade both the central nervous system (CNS) (M.S. Xydakis, M.W. Albers, E.H. Holbrook, et al. Lancet 20: 753-761, 2021 https://doi.org/10.1016/S1474-4422(21)00182-4 ) peripheral (PNS) (M.N. Soares, M. Eggelbusch, E. Naddaf, J Cachexia Sarcopenia Muscle 13:11-22, 2022, https://doi.org/10.1002/jcsm.12896), resulting in a variety disorders. This review summarized CNS complications caused by infection, including encephalopathy, neurodegenerative diseases, delirium. Additionally, some PNS disorders such as skeletal muscle damage inflammation, anosmia, smell or taste impairment, myasthenia gravis, Guillain-Barré syndrome, ICU-acquired weakness, post-acute sequelae were described. Furthermore, mechanisms underlying SARS-CoV-2-induced discussed, entering brain through retrograde neuronal hematogenous routes, disrupting normal function cytokine storms, inducing cerebral ischemia hypoxia, thus leading Moreover, an overview long-COVID-19 is provided, along with recommendations for care therapeutic approaches experiencing

Language: Английский

Citations

8
Unravelling the connection between COVID-19 and Alzheimer’s disease: a comprehensive review DOI Creative Commons

Shah Rezlan Shajahan,

Suresh Kumar, Muhammad Danial Che Ramli

et al.

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 8, 2024

Currently, there exists a limited comprehension regarding the correlation between COVID-19 and Alzheimer’s disease (AD). To elucidate interrelationship its impact on outcomes, comprehensive investigation was carried out utilising time-unrestricted searches of reputable databases such as Scopus, PubMed, Web Science, Google Scholar. Our objective to evaluate various medical conditions severe COVID-19-related events. We focused identifying analysing articles that discussed clinical characteristics patients, particularly those pertaining events ICU admission, mechanical ventilation, pneumonia, mortality acute respiratory distress syndrome (ARDS) serious lung condition causes low blood oxygen. Through careful data analysis information gathering, we tried figure how likely it people with conditions, like AD, would have research investigated potential mechanisms link AD COVID-19. The ability virus directly invade central nervous system role ACE-2 receptors were investigated. Furthermore, OAS1 gene served genetic In context COVID-19, our findings suggest individuals may be more susceptible experiencing outcomes. Consequently, is crucial provide personalised care management for this demographic. Further required attain intricate well ramifications patient

Language: Английский

Citations

6
Microfluidic Isolation of Neuronal-Enriched Extracellular Vesicles Shows Distinct and Common Neurological Proteins in Long COVID, HIV Infection and Alzheimer’s Disease DOI Open Access
Lynn Pulliam,

Bing Sun,

Erin McCafferty

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3830 - 3830

Published: March 29, 2024

Long COVID (LongC) is associated with a myriad of symptoms including cognitive impairment. We reported at the beginning COVID-19 pandemic that neuronal-enriched or L1CAM+ extracellular vesicles (nEVs) from people LongC contained proteins Alzheimer’s disease (AD). Since time, subset prior infection continue to report neurological problems more than three months after infection. Blood markers better characterize are elusive. To further identify neuronal LongC, we maximized number nEVs isolated plasma by developing hybrid EV Microfluidic Affinity Purification (EV-MAP) technique. and complaints, AD, HIV mild Using OLINK platform assesses 384 proteins, identified 11 significant increased in 2 decreased (BST1, GGT1). Fourteen were AD forty impairment elevated one (IVD). One common protein (BST1) was HIV. Six (MIF, ENO1, MESD, NUDT5, TNFSF14 FYB1) expressed both no AD. This study begins differences similarities response versus

Language: Английский

Citations

6
Melatonin: a ferroptosis inhibitor with potential therapeutic efficacy for the post-COVID-19 trajectory of accelerated brain aging and neurodegeneration DOI Creative Commons
Asmaa Yehia, Osama A. Abulseoud

Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)

Published: April 19, 2024

Abstract The unprecedented pandemic of COVID-19 swept millions lives in a short period, yet its menace continues among survivors the form post-COVID syndrome. An exponentially growing number suffer from cognitive impairment, with compelling evidence trajectory accelerated aging and neurodegeneration. novel enigmatic nature this yet-to-unfold pathology demands extensive research seeking answers for both molecular underpinnings potential therapeutic targets. Ferroptosis, an iron-dependent cell death, is strongly proposed underlying mechanism post-COVID-19 neurodegeneration discourse. incites neuroinflammation, iron dysregulation, reactive oxygen species (ROS) accumulation, antioxidant system repression, renin-angiotensin (RAS) disruption, clock gene alteration. These events pave way ferroptosis, which shows signature COVID-19, premature aging, neurodegenerative disorders. In search treatment, melatonin shines as promising ferroptosis inhibitor repeatedly reported safety tolerability. According to various studies, has proven efficacy attenuating severity certain manifestations, validating reputation anti-viral compound. Melatonin well-documented anti-aging properties combating neurodegenerative-related pathologies. can block leading since it efficient anti-inflammatory, chelator, antioxidant, angiotensin II antagonist, regulator. Therefore, we propose culprit behind melatonin, well-fitting inhibitor, treatment.

Language: Английский

Citations

6
Malignant Brain Aging: The Formidable Link Between Dysregulated Signaling Through Mechanistic Target of Rapamycin Pathways and Alzheimer’s Disease (Type 3 Diabetes) DOI
Suzanne M. de la Monte

Journal of Alzheimer s Disease, Journal Year: 2023, Volume and Issue: 95(4), P. 1301 - 1337

Published: Sept. 12, 2023

Malignant brain aging corresponds to accelerated age-related declines in functions eventually derailing the self-sustaining forces that govern independent vitality. establishes path toward dementing neurodegeneration, including Alzheimer's disease (AD). The full spectrum of AD includes progressive dysfunction neurons, oligodendrocytes, astrocytes, microglia, and microvascular systems, is mechanistically driven by insulin insulin-like growth factor (IGF) deficiencies resistances with accompanying deficits energy balance, increased cellular stress, inflammation, impaired perfusion, mimicking core features diabetes mellitus. underlying pathophysiological derangements result mitochondrial dysfunction, abnormal protein aggregation, oxidative endoplasmic reticulum aberrant autophagy, post-translational modification proteins, all which are signature both dysregulated insulin/IGF-1-mechanistic target rapamycin (mTOR) signaling. This article connects dots from benign malignant neurodegeneration reviewing salient pathologies associated initially adaptive later dysfunctional mTOR signaling brain. Effective therapeutic preventive measures must be two-pronged designed 1) address complex shifting impairments through re-purpose effective anti-diabetes therapeutics brain, 2) minimize impact extrinsic mediators transitions, e.g., inflammatory states, obesity, systemic resistance diseases, repeated bouts general anesthesia, minimizing exposures or implementing neuroprotective measures.

Language: Английский

Citations

14
Investigating the structural network underlying brain-immune interactions using combined histopathology and neuroimaging: a critical review for its relevance in acute and long COVID-19 DOI Creative Commons
Zora Kikinis, Agustín Castañeyra-Perdomo, José Luis González–Mora

et al.

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15

Published: March 25, 2024

Current views on immunity support the idea that extends beyond defense functions and is tightly intertwined with several other fields of biology such as virology, microbiology, physiology ecology. It also critical for our understanding autoimmunity cancer, two topics great biological relevance public health considerations disease prevention treatment. Central to this review, immune system known interact intimately nervous has been recently hypothesized be involved not only in autonomic limbic bio-behaviors but cognitive function. Herein we review structural architecture brain network response. Furthermore, elaborate upon implications inflammatory processes affecting brain-immune interactions reported pathological conditions due SARS-Cov-2 virus infection, namely acute post-acute COVID-19. Moreover, discuss how current neuroimaging techniques combined ad hoc clinical autopsies histopathological analyses could critically affect validity translation studies human using neuroimaging. Advances are expected translate into novel therapeutic avenues a vast array domains including autoimmune diseases or viral infections Long

Language: Английский

Citations

5
Promising Strategies to Reduce the SARS-CoV-2 Amyloid Deposition in the Brain and Prevent COVID-19-Exacerbated Dementia and Alzheimer’s Disease DOI Creative Commons
Nikita Navolokin,

Viktoria Adushkina,

Daria Zlatogorskaya

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(6), P. 788 - 788

Published: June 16, 2024

The COVID-19 pandemic, caused by infection with the SARS-CoV-2 virus, is associated cognitive impairment and Alzheimer’s disease (AD) progression. Once it enters brain, virus stimulates accumulation of amyloids in brain that are highly toxic to neural cells. These may trigger neurological symptoms COVID-19. meningeal lymphatic vessels (MLVs) play an important role removal toxins mediate viral drainage from brain. MLVs considered a promising target prevent COVID-19-exacerbated dementia. However, there limited methods for augmentation MLV function. This review highlights new discoveries field COVID-19-mediated amyloid development strategies stimulate clearance through other pathways. based on innovative treating dysfunction induced infection, including use photobiomodulation, plasmalogens, medicinal herbs, which offer hope addressing challenges posed virus.

Language: Английский

Citations

5
The Inflammation-Induced Dysregulation of Reelin Homeostasis Hypothesis of Alzheimer’s Disease DOI
Brady S. Reive, Victor Lau, Carla L. Sánchez-Lafuente

et al.

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: 100(4), P. 1099 - 1119

Published: July 12, 2024

Alzheimer's disease (AD) accounts for most dementia cases, but we lack a complete understanding of the mechanisms responsible core pathology associated with (e.g., amyloid plaque and neurofibrillary tangles). Inflammation has been identified as key contributor AD pathology, recent evidence pointing towards Reelin dysregulation being inflammation. Here describe signaling outline existing research involving in Research is described pertaining to inflammatory immunological functions before propose mechanism through which inflammation renders susceptible resulting induction exacerbation pathology. Based on this hypothesis, it predicted that disorders both (including peripheral neuroinflammation) upregulated expression downregulation) have elevated risk developing AD. We conclude description various

Language: Английский

Citations

5
COVID-19 and Alzheimer’s Disease Share Common Neurological and Ophthalmological Manifestations: A Bidirectional Risk in the Post-Pandemic Future DOI Creative Commons
Giuseppina Amadoro, Valentina Latina,

Egidio Stigliano

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(22), P. 2601 - 2601

Published: Nov. 10, 2023

A growing body of evidence indicates that a neuropathological cross-talk takes place between the coronavirus disease 2019 (COVID-19) -the pandemic severe pneumonia has had tremendous impact on global economy and health since three years after its outbreak in December 2019- Alzheimer’s Disease (AD), leading cause dementia among human beings, reaching 139 million by year 2050. Even though COVID-19 is primary respiratory disease, causative agent, so-called Severe Acute Respiratory Syndrome 2 (SARS-CoV-2), also endowed with high neuro-invasive potential (Neurocovid). The neurological complications COVID-19, resulting from direct viral entry into Central Nervous System (CNS) and/or indirect systemic inflammation dysregulated activation immune response, encompass memory decline anosmia which are typically associated AD symptomatology. In addition, patients diagnosed more vulnerable to SARS-CoV-2 infection inclined clinical outcomes. present review, we better elucidate intimate connection summarizing involved risk factors/targets underlying biological mechanisms shared these two disorders particular focus Angiotensin-Converting Enzyme (ACE2) receptor, APOlipoprotein E (APOE), aging, neuroinflammation cellular pathways Amyloid Precursor Protein (APP)/Amyloid beta (Aβ) tau neuropathologies. Finally, involvement ophthalmological manifestations, including vitreo-retinal abnormalities visual deficits, both discussed. Understanding common physiopathological aspects linking will pave way novel management diagnostic/therapeutic approaches cope them post-pandemic future.

Language: Английский

Citations

10
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

Citations

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