Phosphorylated-tau associates with HSV-1 chromatin and correlates with nuclear speckles decondensation in low-density host chromatin regions DOI Creative Commons
Leonardo D’Aiuto,

Jill K. Caldwell,

Terri G. Edwards

et al.

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106804 - 106804

Published: Jan. 1, 2025

Abnormal tau phosphorylation is a key mechanism in neurodegenerative diseases. Evidence implicates infectious agents, such as Herpes Simplex Virus 1 (HSV-1), co-factors the onset or progression of diseases, including Alzheimer's disease. This has led to divergence field regarding contribution viruses etiology Research indicates that may function risk factors driving disease rather than playing causative role. Investigating HSV-1 abnormal important for understanding role agents neurodegeneration. We generated cellular models acute, latent infection, and viral reactivation from latency cortical brain organoids investigated interplay between infection by employing human induced pluripotent stem cell (iPSC)-derived monolayer neuronal cultures organoids. Acute with strains 17syn+ KOS caused nuclear accumulation phosphorylated (p-tau) neurons neural precursor cells. Antivirals prevented p-tau. Viral was accompanied translocation Chromatin immunoprecipitation analysis indicated an interaction p-tau chromatin. A reduction abundance component speckles their loss organized morphology low host chromatin density regions observed, strain-specific differences. followed increase BRSKs TAOKs, kinases known phosphorylate tau. These findings show demonstrate ability activate mechanisms are observed

Language: Английский

Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission DOI
Gill Livingston, Jonathan Huntley, Kathy Liu

et al.

The Lancet, Journal Year: 2024, Volume and Issue: 404(10452), P. 572 - 628

Published: July 31, 2024

Language: Английский

Citations

559
Solving the puzzle of Long Covid DOI Open Access
Ziyad Al‐Aly, Eric J. Topol

Science, Journal Year: 2024, Volume and Issue: 383(6685), P. 830 - 832

Published: Feb. 22, 2024

Long Covid provides an opportunity to understand how acute infections cause chronic disease

Language: Английский

Citations

65
The role of peripheral inflammatory insults in Alzheimer’s disease: a review and research roadmap DOI Creative Commons
Keenan A. Walker, Lydia M. Le Page, Niccolò Terrando

et al.

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: June 5, 2023

Abstract Peripheral inflammation, defined as inflammation that occurs outside the central nervous system, is an age-related phenomenon has been identified a risk factor for Alzheimer’s disease. While role of chronic peripheral well characterized in context dementia and other conditions, less known about neurologic contribution acute inflammatory insults take place system. Herein, we define immune challenge form pathogen exposure (e.g., viral infection) or tissue damage surgery) causes large, yet time-limited, response. We provide overview clinical translational research examined connection between disease, focusing on three categories have received considerable attention recent years: infection, critical illness, surgery. Additionally, review neurobiological mechanisms which facilitate neural response to discuss potential blood–brain barrier components neuro-immune axis After highlighting knowledge gaps this area research, propose roadmap address methodological challenges, suboptimal study design, paucity transdisciplinary efforts thus far limited our understanding how pathogen- damage-mediated may contribute Finally, therapeutic approaches designed promote resolution be used following preserve brain health limit progression neurodegenerative pathology.

Language: Английский

Citations

49
Chronic effects of inflammation on tauopathies DOI

Connor Langworth-Green,

Saisha Patel,

Zane Jaunmuktane

et al.

The Lancet Neurology, Journal Year: 2023, Volume and Issue: 22(5), P. 430 - 442

Published: April 13, 2023

Language: Английский

Citations

46
Anti-herpetic tau preserves neurons via the cGAS-STING-TBK1 pathway in Alzheimer’s disease DOI Creative Commons

Vanesa R. Hyde,

Chaoming Zhou,

J R Muñóz y Fernández

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: unknown, P. 115109 - 115109

Published: Jan. 1, 2025

Alzheimer's disease (AD) diagnosis relies on the presence of extracellular β-amyloid (Aβ) and intracellular hyperphosphorylated tau (p-tau). Emerging evidence suggests a potential link between AD pathologies infectious agents, with herpes simplex virus 1 (HSV-1) being leading candidate. Our investigation, using metagenomics, mass spectrometry, western blotting, decrowding expansion pathology, detects HSV-1-associated proteins in human brain samples. Expression herpesvirus protein ICP27 increases severity strongly colocalizes p-tau but not Aβ. Modeling organoids shows that HSV-1 infection elevates phosphorylation. Notably, reduces expression markedly decreases post-infection neuronal death from 64% to 7%. This modeling prompts investigation into cGAS-STING-TBK1 pathway products, nuclear factor (NF)-κB IRF-3, which AD. Furthermore, experimental activation STING enhances phosphorylation, while TBK1 inhibition prevents it. Together, these findings suggest phosphorylation acts as an innate immune response AD, driven by cGAS-STING.

Language: Английский

Citations

9
Shattering the Amyloid Illusion: The Microbial Enigma of Alzheimer’s Disease Pathogenesis—From Gut Microbiota and Viruses to Brain Biofilms DOI Creative Commons
Anna Onisiforou, Eleftheria G. Charalambous, Panos Zanos

et al.

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

Citations

4
Data‐driven discovery of associations between prescribed drugs and dementia risk: A systematic review DOI Creative Commons
Benjamin R. Underwood, Ilianna Lourida, Jessica Gong

et al.

Alzheimer s & Dementia Translational Research & Clinical Interventions, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 1, 2025

Language: Английский

Citations

2
Plasma proteomic evidence for increased β-amyloid pathology after SARS-CoV-2 infection DOI Creative Commons
Eugene Duff,

Henrik Zetterberg,

Amanda Heslegrave

et al.

Nature Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Abstract Previous studies have suggested that systemic viral infections may increase risks of dementia. Whether this holds true for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is unknown. Determining important anticipating the potential future incidence To begin to do this, we measured plasma biomarkers linked Alzheimer’s disease pathology in UK Biobank before and after serology-confirmed SARS-CoV-2 infections. infection was associated with β-amyloid pathology: reduced Aβ42:Aβ40 ratio and, more vulnerable participants, lower Aβ42 higher pTau-181. The biomarker changes were greater participants who had been hospitalized COVID-19 or reported hypertension previously. We showed brain structural imaging patterns disease, cognitive test scores poorer overall health evaluations. Our data from post hoc case–control matched study thus provide observational evidence can be older adults. While these results not establish causality, they suggest (and possibly other inflammatory diseases) risk disease.

Language: Английский

Citations

2
The amyotrophic lateral sclerosis exposome: recent advances and future directions DOI
Stephen A. Goutman, Masha G. Savelieff,

Dae-Gyu Jang

et al.

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(10), P. 617 - 634

Published: Sept. 14, 2023

Language: Английский

Citations

40
Viral pathogens increase risk of neurodegenerative disease DOI Open Access

Britanie M. Blackhurst,

Kristen E. Funk

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(5), P. 259 - 260

Published: March 2, 2023

Language: Английский

Citations

39