Viral Infections, Are They a Trigger and Risk Factor of Alzheimer’s Disease?

Pathogens, Journal Year: 2024, Volume and Issue: 13(3), P. 240 - 240

Published: March 8, 2024

Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed currently affected. Many causation hypotheses AD exist, yet intriguing link between viral infection its possible contribution known etiology has become an attractive focal point research for field challenging study task. In this review, we will explore historical perspective milestones that led investigate connection AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), severe cute respiratory syndrome coronavirus 2 (SARS-CoV-2), along others mentioned, include various presently considered within field. We delve into strong evidence implicating these in development lytic replication axonal transport HSV-1, mechanisms ZIKV neurotropism through human protein Musashi-1 (MSI1), spread SARS-CoV-2 transfer BBB endothelial cells glial then neurons via transsynaptic transfer. also beyond mere associations by carefully analyzing potential which may contribute pathology. This includes but not limited direct neuronal infections, dysregulation immune responses, impact on processing (Aβ42 hyperphosphorylated tau). Controversies challenges virus–AD relationship emerge tease out mechanisms. Looking forward, emphasize future directions, distinct questions proposed experimentations explore, should take tackle remaining unanswered glaring gaps persist. Overall, review aims provide comprehensive survey past, present, infections their association while encouraging further discussion.

Language: Английский

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Virology—The next fifty years

Cell, Journal Year: 2024, Volume and Issue: 187(19), P. 5128 - 5145

Published: Sept. 1, 2024

Language: Английский

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Immunological Profile and Markers of Endothelial Dysfunction in Elderly Patients with Cognitive Impairments

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1888 - 1888

Published: Feb. 4, 2024

The process of aging is accompanied by a dynamic restructuring the immune response, phenomenon known as immunosenescence. Further, damage to endothelium can be both cause and consequence many diseases, especially in elderly people. purpose this study was carry out immunological biochemical profiling people with acute ischemic stroke (AIS), chronic cerebral circulation insufficiency (CCCI), prediabetes or newly diagnosed type II diabetes mellitus (DM), subcortical vascular dementia (SIVD). Socio-demographic, lifestyle, cognitive data were obtained. Biochemical, hematological, analyses carried out, extracellular vesicles (EVs) endothelial CD markers assessed. greatest number significant deviations from conditionally healthy donors (HDs) same age registered SIVD group, total 20, which 12 specific six non-specific but maximal differences (as compared other three groups) HDs group. for MOCA (Montreal Cognitive Impairment Scale), MMSE (Mini Mental State Examination) life satisfaction self-assessment scores, decrease albumin levels, ADAMTS13 (a Disintegrin Metalloproteinase Thrombospondin Type 1 motif, member 13) activity, an increase VWF (von Willebrand factor) level. Considering changes parameters (mostly Th17-like cells) (CD144 CD34), repair impaired extent DM AIS patients showed HD controls, including These high NEFAs (non-esterified fatty acids) CD31 CD147 EVs. lowest CCCI nine total. There controls no specifics just one difference control parameters, α1-AGP (alpha acid glycoprotein, orosomucoid). Besides patients, impairments also complete absence such (SIVD group). On hand, microvascular seemed latter considering indicators ADAMTS13. In maximum response registered, mainly cells. reaction not pronounced groups may indicate initial stages and/or compensatory nature organic (remodeling). At time, indicated persistent remodeling microvessels, inflammation, anabolic function liver tissues. obtained support two interrelated assumptions. Taking into account primary factors that trigger pathological processes associated pathology related first assumption purine degradation skeletal muscle major factor production uric acid, followed its non-muscle cells, main are Another therapeutic levels progenitor cells have effect reducing risk cerebrovascular disease neurodegenerative diseases.

Language: Английский

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Alzheimer's disease and herpes viruses: Current events and perspectives

Reviews in Medical Virology, Journal Year: 2024, Volume and Issue: 34(3)

Published: May 1, 2024

Alzheimer's disease (AD) is a real and current scientific societal challenge. characterised by neurodegenerative neuroinflammatory process, but the etiopathogenetic mechanisms are still unclear. The possible infectious aetiology potential involvement of Herpes viruses as triggers for formation extracellular deposits amyloid beta (Aβ) peptide (amyloid plaques) intraneuronal aggregates hyperphosphorylated misfold could be explanation. In fact, genetic interference with genome host neuronal cell or stimulation infection to continuous immune response consequent chronic inflammation constitute those underlying development AD, implications in understanding management disease. significantly involved pathogenesis AD particular, their ability reactivate particular conditions such immunocompromise immunosenescence, explain neurological damage characteristic AD. Our review aims evaluate state art knowledge perspectives regarding relationship between order able identify therapeutic implications.

Language: Английский

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Molecular mechanisms and therapeutic potential of lithium in Alzheimer’s disease: repurposing an old class of drugs

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

Published: July 11, 2024

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss. Despite advances in understanding the pathophysiological mechanisms of AD, effective treatments remain scarce. Lithium salts, recognized as mood stabilizers bipolar disorder, have been extensively studied for their neuroprotective effects. Several studies indicate that lithium may be disease-modifying agent treatment AD. Lithium’s properties AD acting on multiple neuropathological targets, such reducing amyloid deposition tau phosphorylation, enhancing autophagy, neurogenesis, synaptic plasticity, regulating cholinergic glucose metabolism, inhibiting neuroinflammation, oxidative stress, apoptosis, while preserving mitochondrial function. Clinical trials demonstrated therapy can improve function patients with In particular, meta-analyses shown more safer than recently FDA-approved aducanumab improving The affordability therapeutic efficacy prompted reassessment its use. However, use lead to potential side effects safety issues, which limit clinical application. Currently, several new formulations are undergoing efficacy. This review focuses lithium’s mechanism action treating highlighting latest preclinical trials. It also explores coping strategies, offering strategy

Language: Английский

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Navigating the GSK-3β inhibitors as versatile multi-target drug ligands in Alzheimer’s disease intervention – A comprehensive review

Results in Chemistry, Journal Year: 2024, Volume and Issue: 7, P. 101500 - 101500

Published: Jan. 1, 2024

Alzheimer's disease (AD) remains a significant global health challenge, necessitating the exploration of novel therapeutic strategies. AD is neurodegenerative characterized by formation amyloid-β (Aβ) plaques and neurofibrillary tangles composed tau protein. It stated to be cause multiple mechanistic pathways biochemical events, hence, targeting only one mechanism at time cannot suffice for all-round therapy. A multi-target drug ligand strategy can thus employed in such setting modulate targets simultaneously. Glycogen synthase kinase-3β (GSK-3β) an enzyme involved hyperphosphorylation, neuroinflammation, maintaining neuronal plasticity, various cell processes. Thus, inhibiting GSK-3β itself may help control some key factors responsible pathophysiology. This review comprehensively evaluates potential inhibitors as ligands therapeutics. We discuss molecular mechanisms pathology preclinical clinical evidence supporting efficacy ameliorating cognitive decline pathological hallmarks AD. Furthermore, we explore challenges associated with GSK-3β, selectivity, blood–brain barrier penetration, adverse effects. Additionally, highlight recent advances development improved pharmacokinetic properties multitargeting capabilities. Finally, future directions implications complex landscape

Language: Английский

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Traumatic brain injury alters the effects of class II invariant peptide (CLIP) antagonism on chronic meningeal CLIP + B cells, neuropathology, and neurobehavioral impairment in 5xFAD mice

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: June 27, 2024

Abstract Background Traumatic brain injury (TBI) is a significant risk factor for Alzheimer’s disease (AD), and accumulating evidence supports role adaptive immune B T cells in both TBI AD pathogenesis. We previously identified cell major histocompatibility complex class II (MHCII)-associated invariant chain peptide (CLIP)-positive expansion after TBI. also showed that antagonizing CLIP binding to the antigen presenting groove of MHCII acutely reduced + splenic was neuroprotective. The current study investigated chronic effects 5xFAD mouse model, with without Methods 12-week-old male wild type (WT) mice were administered either antagonist (CAP) or vehicle, once at 30 min sham lateral fluid percussion (FPI). Analyses included flow cytometric analysis dural meninges spleen, histopathological brain, magnetic resonance diffusion tensor imaging, cerebrovascular analysis, assessment motor neurobehavioral function over ensuing 6 months. Results 9-month-old had significantly more compared age-matched WT mice. A one-time treatment CAP this population Importantly, improved some immune, histopathological, impairments six Although FPI did not further elevate meningeal cells, it negate ability reduce 3 months age exacerbated aspects pathology mice, including reducing hippocampal neurogenesis, increasing plaque deposition CA3, altering microgliosis, disrupting structure. ameliorated but all these effects.

Language: Английский

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Development of a high-throughput, quantitative platform using human cerebral organoids to study virus-induced neuroinflammation in Alzheimer’s disease

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 23, 2024

ABSTRACT Neuroinflammation is a central process in the pathogenesis of several neurodegenerative diseases such as Alzheimer’s disease (AD), and there are active efforts to target pathways involved neuroinflammation for molecular biomarker discovery therapeutic development diseases. It was also proposed that may be an infectious etiology AD associated with viruses herpes simplex virus (HSV-1) influenza A (IAV), leading neuroinflammation-induced or progression. We sought develop high-throughput, quantitative assays using dissociated cells from human cerebral organoids (dcOrgs), can used screening compounds reverse AD-associated neuroinflammation. found HSV-1 infection, but not IAV dcOrgs led increased intracellular Aβ42 phosphorylated Tau-Thr212 (pTau-212) expression, lower ratios secreted Aβ42/40, well neuronal loss, proportions astrocytes microglia, which hallmarks AD. Among glia cell-type markers, Iba1 (microglia) GFAP (astrocyte) expression were most strongly correlated further supported these biomarkers perturbed by glia-mediated By performing large-scale RNA sequencing, we observed differentially expressed transcripts infected specifically enriched GWAS genes, genes other common neurodegenerative, neuropsychiatric autoimmune Immediate treatment anti-herpetic drug acyclovir (ACV) rescued cellular transcriptomic dosage-dependent manner, indicating it possible use our high-throughput platform identify

Language: Английский

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A Brief History of the Progress in Our Understanding of Genetics and Lifestyle, Especially Diet, in the Risk of Alzheimer’s Disease

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: 100(s1), P. S165 - S178

Published: Aug. 6, 2024

The two major determining factors for Alzheimer's disease (AD) are genetics and lifestyle. Alleles of the apolipoprotein E (APOE) gene play important roles in development late-onset AD, with APOEɛ4 increasing risk, APOEɛ3 being neutral, APOEɛ2 reducing risk. Several modifiable lifestyle have been studied terms how they can modify risk AD. Among these dietary pattern, nutritional supplements such as omega-3 fatty acids, B vitamins, physical exercise, obesity, vitamin D. Western diet increases while patterns Mediterranean vegetarian/vegan diets reduce Foods associated reduced include coffee, fruits vegetables, whole grains legumes, fish, meat ultraprocessed foods increased especially when lead to obesity. In multi-country ecological studies, amount national has highest correlation history research regarding on AD is emphasized this review. be modified starting at least by mid-life. People greater genetic would benefit more choosing and/or delay incidence

Language: Английский

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Infection burden, periodontal pathogens, and their interactive association with incident all‐cause and Alzheimer's disease dementia in a large national survey

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(9), P. 6468 - 6485

Published: Aug. 8, 2024

Abstract INTRODUCTION Relationships and interplay of an infection burden (IB) periodontal pathogens or disease (Pd) markers with Alzheimer's (AD) all‐cause dementia among US adults were examined. METHODS Less than equal to 2997 participants from the National Health Nutrition Survey III linked CMS‐Medicare [≥45 years (1988‐1994); ≤30 follow‐up]. RESULTS Hepatitis C (hazard ratio = 3.33, p 0.004) herpes simplex virus 2 strongly associated greater risk. Porphyromonas gingivalis Streptococcus oralis AD risk at higher IB. The red‐green pathogen cluster coupled IB count increased minority racial groups. Pocket probing depth lower in overall sample. DISCUSSION Select viruses bacteria dementia, while interacted Pd relation these outcomes. Highlights Interplay was tested. ≤2997 NHANES Medicare. Tetanus sero‐positivity Red‐green high IB, minorities.

Language: Английский

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