Shattering the Amyloid Illusion: The Microbial Enigma of Alzheimer’s Disease Pathogenesis—From Gut Microbiota and Viruses to Brain Biofilms

Microorganisms, Journal Year: 2025, Volume and Issue: 13(1), P. 90 - 90

Published: Jan. 5, 2025

For decades, Alzheimer's Disease (AD) research has focused on the amyloid cascade hypothesis, which identifies amyloid-beta (Aβ) as primary driver of disease. However, consistent failure Aβ-targeted therapies to demonstrate efficacy, coupled with significant safety concerns, underscores need rethink our approach AD treatment. Emerging evidence points microbial infections environmental factors in pathoetiology. Although a definitive causal link remains unestablished, collective is compelling. This review explores unconventional perspectives and emerging paradigms regarding involvement pathogenesis, emphasizing gut-brain axis, brain biofilms, oral microbiome, viral infections. Transgenic mouse models show that gut microbiota dysregulation precedes Aβ accumulation, signaling pathways. Viral like Herpes Simplex Virus Type 1 (HSV-1) Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may lead by modulating host processes immune system. peptide's antimicrobial function response infection might inadvertently promote AD. We discuss potential microbiome-based promising strategies for managing potentially preventing progression. Fecal transplantation (FMT) restores balance, reduces improves cognition preclinical models. Probiotics prebiotics reduce neuroinflammation plaques, while antiviral targeting HSV-1 vaccines shingles vaccine mitigate pathology. Developing effective treatments requires standardized methods identify measure patients, enabling personalized address individual contributions pathogenesis. Further needed clarify interactions between microbes Aβ, explore bacterial interplay, understand their broader effects translate these insights into clinical interventions.

Language: Английский

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Alzheimer’s disease and antibody-mediated immune responses to infectious diseases agents: a mendelian randomization study

Hereditas, Journal Year: 2025, Volume and Issue: 162(1)

Published: Jan. 4, 2025

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder, with antibody-mediated immune responses to infectious diseases agents potentially playing decisive role in its pathophysiological process. However, the causal relationship between antibodies and AD remains unclear.

Language: Английский

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HSV-1 virions and related particles: biogenesis and implications in the infection

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

ABSTRACT Virion formation and egress are sophisticated processes that rely on the spatial temporal organization of host cell membranes manipulation machineries involved in protein sorting, membrane bending, fusion, fission. These result infectious virions, defective particles, various vesicle-like structures. In herpes simplex virus 1 (HSV-1) infections, virions capsid-less known as light (L)-particles, formed. HSV-1 infection also stimulates release particles resemble extracellular vesicles (EVs). productively infected cells, most EVs generated through CD63 tetraspanin biogenesis pathway lack viral components. A smaller subset EVs, endosomal sorting complexes required for transport (ESCRT) pathway, contains both factors. Viral mechanisms tightly regulate EV biogenesis, including inhibition autophagy—a process critical increased production CD63+ during infection. Mutant viruses fail to suppress autophagy instead promote microvesicle from plasma membrane. Additionally, ICP0 (Infected Cell Protein 0) enhances The different types can be separated by density gradients due their distinct biophysical properties. L-particles ESCRT+ display a pro-viral role, supporting replication, whereas exhibit antiviral effects. Overall, these studies highlight yields numerous diverse with type composition shaped ability evade responses. likely shape microenvironment determine disease outcomes.

Language: Английский

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Increased risk of dementia associated with herpes simplex virus infections: Evidence from a retrospective cohort study using U.S. electronic health records

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 16, 2025

Background: Alzheimer's disease is the most common age-related dementia. Recent compelling evidence from previous retrospective electronic health record (EHRs) studies suggests that herpes simplex virus (HSV) infections may be a risk factor for developing However, no age and propensity score matched have been published in United States general population cohort study to date. Objective: We aimed identify whether HSV infection shows significantly increased of development dementia sizable heterogeneous cohort. investigated type 1 (HSV1), 2 (HSV2), or coinfections with both serotypes pose greater across different biological sexes racial groups. Methods: EHRs patients history specific (HSV1 HSV2) were selected analysis. These records compared propensity-matched control group analyzed hazard odds ratios through TriNetX. Results: There was significant difference incidence HSV-infected versus control. Individuals HSV, HSV1, HSV2, coinfection all showed controls. Males HSV2 are at higher outcome than females HSV2. Conclusions: While consistent reports, these findings first establish who any diagnosis using nationwide, population-based States.

Language: Английский

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Infectious Disease as a Modifiable Risk Factor for Dementia: A Narrative Review

Pathogens, Journal Year: 2024, Volume and Issue: 13(11), P. 974 - 974

Published: Nov. 7, 2024

This narrative review examines infectious diseases as modifiable risk factors for dementia, particularly in the context of an aging global population. As prevalence Alzheimer's disease and related dementias is expected to rise, prevention has become increasingly important due limited efficacy current treatments. Emerging evidence links specific increased dementia risk, possibly through mechanisms like neuroinflammation disruption normal cell function. Here, we findings on how viral bacterial infections contribute explore potentially preventive measures, including vaccinations antiviral Studies indicate that against influenza, herpes zoster, hepatitis, well treatments targeting human herpesvirus, could reduce incidence dementia. Additionally, non-pharmaceutical interventions during pandemics long-term care settings are highlighted effective strategies reducing spread diseases, lowering risk. Putative underlying protective effects these suggest systemic inflammation may be their efficacy. While currently available suggests at best association between some this emphasizes need incorporate into broader public health mitigate growing burden Further research required measures across diverse populations deepen our understanding biological involved.

Language: Английский

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Human in vivo evidence of associations between herpes simplex virus and cerebral amyloid-beta load in normal aging

Alzheimer s Research & Therapy, Journal Year: 2024, Volume and Issue: 16(1)

Published: April 3, 2024

Abstract Background Mounting data suggests that herpes simplex virus type 1 (HSV-1) is involved in the pathogenesis of AD, possibly instigating amyloid-beta (Aβ) accumulation decades before onset clinical symptoms. However, human vivo evidence linking HSV-1 infection to AD pathology lacking normal aging, which may contribute elucidation role as a potential risk factor. Methods To shed light into this question, serum anti-HSV IgG levels were correlated with 18 F-Florbetaben-PET binding Aβ deposits and blood markers neurodegeneration (pTau181 neurofilament chain) cognitively older adults. Additionally, we investigated whether associations between more evident APOE4 carriers. Results We showed increased are associated higher load fronto-temporal regions Remarkably, these cortical exhibited abnormal patterns resting state-functional connectivity (rs-FC) only those individuals showing highest IgG. further found positive relationships load, particularly anterior cingulate cortex, moderated by genotype, strongest genetic factor for AD. Importantly, unrelated either subclinical cognitive deficits or neurodegeneration. Conclusions All together, results suggest HSV selectively related deposition supporting inclusion adults prospective trials antimicrobial therapy aimed at decreasing aging population.

Language: Английский

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Differences in safety profiles of anti-herpesvirus medications: a real-world pharmacovigilance study based on the FAERS database

Expert Opinion on Drug Safety, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 10

Published: Oct. 8, 2024

Background Anti-herpesvirus drug safety profiles have not been systematically compared. Understanding variations in adverse events (AEs) could provide reference for rational clinical use.

Language: Английский

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