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 infectious agents: a comprehensive review of pathogenic mechanisms and microRNA roles

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 18

Published: Jan. 7, 2025

Alzheimer's Disease (AD) is the most prevalent type of dementia and characterized by presence senile plaques neurofibrillary tangles. There are various theories concerning causes AD, but connection between viral bacterial infections their potential role in pathogenesis AD has become a fascinating area research for field. Various viruses such as Herpes simplex virus 1 (HSV-1), Epstein-Barr (EBV), Cytomegalovirus (CMV), influenza viruses, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), well bacteria Chlamydia pneumoniae (CP), Helicobacter pylori (HP), Porphyromonas gingivalis (P. gingivalis), Spirochetes eukaryotic unicellular parasites (e.g., Toxoplasma gondii), have been linked to due ability activate immune system, induce inflammation increase oxidative stress, thereby leading cognitive decline AD. In addition, microRNAs (miRNAs) might play crucial mechanisms these pathogens since they utilized target protein-coding genes, allowing evasion, maintaining latency, suppressing cellular signaling molecules. Also, can regulate gene expression human cells. This article provides an overview association infectious agents, with focus on which may be related These findings suggest important areas further explored future studies.

Language: Английский

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HIV-1 infection facilitates Alzheimer’s disease pathology in humanized APP knock-in immunodeficient mice

NeuroImmune Pharmacology and Therapeutics, Journal Year: 2025, Volume and Issue: 4(1), P. 27 - 38

Published: Feb. 8, 2025

Amyloid-β (Aβ) plaque deposition in the brain is a principal pathological feature of both Alzheimer's disease (AD) and progressive human immunodeficiency virus type one (HIV-1) infection. Both enable Aβ assembly protein aggregation. The potential link between HIV-1 AD remains uncertain, supporting need for reliable animal model. tropic pathogenic humans. It does not replicate mice. restricted species tropism has slowed progress basic research activities. current study seeks to correct model limitations. We created an mouse address develop small that allows studies viral infection by making knock-in (KI) with amyloid precursor (APP)KM670,671NL Swedish mutation genome. resulting founder mice were crossed immunodeficient NOG (NOD. Cg-Prkdc scid Il2rg tm1Sug Tg(CMV-IL-34)1/Jic) generate NOG/APPKM670,671NL/IL-34 (NAIL) reconstituted hematopoietic stem cells NAIL functional adaptive innate immune systems. Four-month-old, humanized infected HIV-1ADA, macrophage-tropic strain then evaluated pathology. Productive was confirmed plasma RNA levels load increased tenfold day 10 25 post-infection. By 25, DNA establishment reservoirs CD45+ from tissues Additionally, p24 measurements lymphoid validated productive Amyloid burden increased. Immunofluorescence staining revealed co-localization fibrils HLA-DR+ microglia These results highlight AD-HIV model's unique pathobiological infectious features where responses can now be measured.

Language: Английский

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The Role of Genetic, Environmental, and Dietary Factors in Alzheimer’s Disease: A Narrative Review

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1222 - 1222

Published: Jan. 30, 2025

Alzheimer’s disease (AD) is one of the most common and severe forms dementia neurodegenerative disease. As life expectancy increases in line with developments medicine, elderly population projected to increase next few decades; therefore, an prevalence some diseases, such as AD, also expected. a result, until radical treatment becomes available, AD expected be more frequently recorded top causes death worldwide. Given current lack cure for only treatments available being ones that alleviate major symptoms, identification contributing factors influence incidence crucial. In this context, genetic and/or epigenetic factors, mainly environmental, disease-related, dietary, or combinations/interactions these are assessed. review, we conducted literature search focusing on environmental air pollution, toxic elements, pesticides, infectious agents, well dietary including various diets, vitamin D deficiency, social (e.g., tobacco alcohol use), variables affected by both behavior gut microbiota. We evaluated studies beneficial effects antibiotics Mediterranean-DASH Intervention Neurodegenerative Delay (MIND) Mediterranean diets.

Language: Английский

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Betrayal From the Core: Centriolar and Cytoskeletal Subversion by Infectious Pathogens

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

Published: Feb. 4, 2025

Microbes and parasites have evolved several means to evade usurp the host cellular machinery mediate pathogenesis. Being major microtubule-organizing center (MTOC) of cell, centrosome is targeted by multiple viral nonviral pathogens their assembly trafficking within cell. This review examines consequence such targeting associated cytoskeletal machinery. We also amassed a substantial body evidence viruses utilizing cilia airway epithelium infection hijacking for efficient entry, replication, egress. While infections been demonstrated induce structural, functional, numerical aberrations in centrosomes, ciliary dysfunction, current literature increasingly supports notion pro-viral role these organelles. Although less explored, impact bacterial parasitic on structures has addressed very briefly. Mechanistically, molecular pathways responsible effects remain largely uncharacterized many instances. Future research focusing centriolar triad comprising centrosome, cilia, satellites will undoubtedly provide vital insights into tactics employed infectious agents subvert centriole cytoskeleton-based

Language: Английский

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Pathogenesis and therapeutic applications of microglia receptors in Alzheimer’s disease

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 14, 2025

Microglia, the resident immune cells of central nervous system, continuously monitor brain’s microenvironment through their array specific receptors. Once brain function is altered, microglia are recruited to sites perform functions, including phagocytosis misfolded proteins, cellular debris, and apoptotic maintain homeostasis. When toxic substances overproduced, over-activated produce large amounts pro-inflammatory cytokines, which induce chronic inflammatory responses lead neurotoxicity. Additionally, can also protect neuronal microglia-neuron crosstalk. Microglia receptors important mediators for receive external stimuli, regulate functional state microglia, transmit signals between cells. In this paper, we first review role microglia-expressed in pathogenesis treatment Alzheimer’s disease; moreover, emphasize complexity targeting therapeutic interventions neurodegenerative disorders inform discovery new biomarkers development innovative therapeutics

Language: Английский

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Herpes simplex virus‐1 infection alters microtubule‐associated protein Tau splicing and promotes Tau pathology in neural models of Alzheimer's disease

Brain Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Herpes simplex virus 1 (HSV-1) infection alters critical markers of Alzheimer's disease (AD) in neurons. One key marker AD is the hyperphosphorylation Tau, accompanied by altered levels Tau isoforms. However, an imbalance these splice variants, specifically resulting from 3R to 4R MAPT splicing exon 10, has yet be directly associated with HSV-1 infection. To this end, we infected 2D and 3D human neural models monitored phosphorylation. Further, transduced SH-SY5Y neurons ICP27, which RNA splicing, analyze if ICP27 alone sufficient induce 10 splicing. We show that induces increasing 4R-Tau protein levels, hyperphosphorylation, oligomerization. Our experiments reveal a novel link between development cytopathic phenotypes linked progression.

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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HSV-1 Infection Alters MAPT Splicing and Promotes Tau Pathology in Neural Models of Alzheimer's Disease

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

Published: Oct. 16, 2024

Herpes simplex virus 1 (HSV-1) infection alters critical markers of Alzheimer's Disease (AD) in neurons. One key marker AD is the hyperphosphorylation Tau, accompanied by altered levels Tau isoforms. However, an imbalance these splice variants, specifically resulting from 3R to 4R

Language: Английский

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Novel Perspectives Focused on the Relationship Between Herpesvirus Encephalitis and Anti-GFAP-Antibody-Positive Astrocytopathy

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 28, 2024

Language: Английский

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