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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Associations of infections and vaccines with Alzheimer's disease point to a role of compromised immunity rather than specific pathogen in AD

Experimental Gerontology, Journal Year: 2024, Volume and Issue: 190, P. 112411 - 112411

Published: April 2, 2024

Diverse pathogens (viral, bacterial, fungal) have been associated with Alzheimer's disease (AD) and related traits in various studies. This suggests that compromised immunity, rather than specific microbes, may play a role AD by increasing an individual's vulnerability to infections, which could contribute neurodegeneration. If true, then vaccines heterologous effects on extending beyond protection against the targeted disease, hold potential for prevention.

Language: Английский

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HDL-based therapeutics: A promising frontier in combating viral and bacterial infections

Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 260, P. 108684 - 108684

Published: July 2, 2024

Language: Английский

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Dual-mode fluorescence and electrochemiluminescence sensors based on Ru-MOF nanosheets for sensitive detection of apoE genes

Journal of Materials Chemistry B, Journal Year: 2023, Volume and Issue: 12(3), P. 701 - 709

Published: Nov. 10, 2023

A fluorescence-electrochemiluminescence (FL-ECL) dual-mode sensor for apoE gene detection has been developed, leveraging the unique properties of ruthenium metal organic framework nanosheets (RuMOFNSs). The system utilizes quenching effect Ru(bpy)

Language: Английский

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Prior infections are associated with smaller hippocampal volume in older women

Frontiers in Dementia, Journal Year: 2024, Volume and Issue: 3

Published: Feb. 7, 2024

Accumulating evidence suggests that infections may play a major role in Alzheimer's disease (AD), however, mechanism is unclear, as multiple pathways be involved. One possibility could contribute to neurodegeneration directly by promoting neuronal death. We explored relationships between history of and brain hippocampal volume (HV), biomarker neurodegeneration, subsample the UK Biobank (UKB) participants. Infectious diagnoses were based on ICD10 codes. The left/right HV was measured magnetic resonance imaging (MRI) cubic millimeters normalized. Analysis variance (ANOVA), Welch test, regression used examine statistical significance. found significantly lower women aged 60–75, well 65–80, years, with infections, compared same age without such history. effect size increased faster for left vs. right HV. Results males didn't reach our study support adult women. detrimental became stronger age, line declining resilience increasing vulnerability stressors due aging. increase observed indicate female verbal memory degrades over time than visual-spatial memory. sex difference reflect higher infection-related factors, which turn risk AD men.

Language: Английский

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APOE4 and infectious diseases jointly contribute to brain glucose hypometabolism, a biomarker of Alzheimer’s pathology: New findings from the ADNI

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0316808 - e0316808

Published: Jan. 7, 2025

Background Impaired brain glucose metabolism is a preclinical feature of neurodegenerative diseases such as Alzheimer’s disease (AD). Infections may promote AD-related pathology. Therefore, we investigated the interplay between infections and APOE4 , strong genetic risk factor for AD. Methods We analyzed data on 1,509 participants in Disease Neuroimaging Initiative (ADNI) database using multivariate linear regression models. The outcomes were rank-normalized hypometabolic convergence index (HCI), statistical regions interest (SROI) AD, mild cognitive impairment (MCI). Marginal mean estimates infections, stratified by carrier status, then computed. Results Prior associated with greater HCI [β = 0.15, 95% CI: 0.03, 0.27, p 0.01]. combined effects carriers levels significantly than either variable alone. Among carriers, estimated marginal was 0.62, rising to 0.77, (p<0.001), indicating an interaction effect. Carriers multiple showed hypometabolism (higher HCI), estimate 0.44 (p 0.01) compared 0.11 0.08) those single infection, revealing dose-response relationship. association SROI AD MCI β -0.01 0.02) 0.04), respectively. Conclusion Our findings suggest that jointly contribute pathology, supporting “multi-hit” mechanism development.

Language: Английский

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The Apoprotein E4 isotype does not affect the severity of COVID-19 infection and other flu-like syndromes

Journal of Medical Microbiology, Journal Year: 2025, Volume and Issue: 74(1)

Published: Jan. 22, 2025

Impact of e4 allele on flu-like syndromes The ɛ4 has no influence syndrome, including COVID-19. COVID-19 severity was associated with BMI, male sex, comorbidities and IL-4 levels.

Language: Английский

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Bibliometric and Visual Analysis of Alzheimer’s Disease and Herpes Simplex Virus Type 1 Infection Between 1990 and 2024

Journal of Multidisciplinary Healthcare, Journal Year: 2025, Volume and Issue: Volume 18, P. 2097 - 2109

Published: April 1, 2025

Recently, some studies suggested that Herpes simplex virus type 1 (HSV-1) infection is an important environmental factor for Alzheimer's disease(AD). The literature on research about HSV-1 and AD emerging. This study used the bibliometric method to investigate relationship between AD. We searched Web of Science Core Collection relevant from 1990 2024. Bibliometric visualization analyses were performed using VOSviewer CiteSpace. From 2024, number publications showed increasing trend. United States made largest contributions in productivity. University Manchester was most productive organization. Professor Ruth F. Itzhaki influential researcher. Journal Disease had published articles. Research mechanisms by which HSV contributes remains a hotspot field, future may further focus antiviral therapeutic strategies targeting infection. Our analysis provides basic information HSV-1. current hotspots this field mainly include mechanism caused HSV-1, drugs treat or prevent

Language: Английский

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Perturbed Lipid Metabolism Transduction Pathways in SARS-CoV-2 Infection and Their Possible Treating Nutraceuticals

Journal of the American Nutrition Association, Journal Year: 2024, Volume and Issue: 43(7), P. 614 - 626

Published: May 28, 2024

The coronavirus disease 2019 (COVID-19) epidemic has evolved into an international public health concern. Its causing agent was SARS-CoV-2 (severe acute respiratory syndrome 2), a lipid bilayer encapsulated virus. Lipids have relevance in the host's viral cycle; additionally; viruses been speculated to manipulate signaling and production influence lipidome of host cells. engages pathways for replication, like fatty acid synthesis activation via upregulation AKT SREBP pathway inhibiting catabolism by AMPK PPAR deactivation. Consequently, lipoprotein levels are altered most cases, i.e., raised LDL, TG, VLDL reduced HDL hyperlipidemic state. Apo lipoproteins, subsiding structural part may also impact spike protein binding cell receptors. In few studies conducted on COVID-19 patients, maintaining shown antiviral activity against infection. It that several potent hypolipidemic drugs, such as statins, hydroxychloroquine, metformin, could be used add-on treatment management. Nutraceuticals Garlic, Fenugreek, vinegar potency lower capability acting these pathways. A link between post-COVID alteration not yet fully understood. this review, we try look over possible modifications metabolism due exposure, besides prospect focusing potential metabolic processes interrupt cycle.

Language: Английский

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Neuroinflammation in Alzheimer’s Disease: A Potential Role of Nose-Picking in Pathogen Entry via the Olfactory System?

Biomolecules, Journal Year: 2023, Volume and Issue: 13(11), P. 1568 - 1568

Published: Oct. 24, 2023

Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by progressive cognitive decline and memory impairment. Many possible factors might contribute to the development of AD, including amyloid peptide tau deposition, but more recent evidence suggests that neuroinflammation may also play an—at least partial—role in its pathogenesis. In years, emerging research has explored involvement external, invading pathogens starting or accelerating neuroinflammatory processes AD. this narrative review, we advance hypothesis AD be partially caused viral, bacterial, fungal entering brain through nose olfactory system. The system represents plausible route for pathogen entry, given direct anatomical connection early stages We discuss potential mechanisms which exploit pathway initiate neuroinflammation, one them being accidental exposure mucosa hands contaminated with soil feces when picking one’s nose.

Language: Английский

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