Inhibition of IFITM3 in cerebrovascular endothelium alleviates Alzheimer's‐related phenotypes

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Abstract INTRODUCTION Interferon‐induced transmembrane protein 3 (IFITM3) modulates γ‐secretase in Alzheimer's Disease (AD). Although IFITM3 knockout reduces amyloid β (Aβ) production, its cell‐specific effect on AD remains unclear. METHODS Single nucleus RNA sequencing (snRNA‐seq) was used to assess expression. Adeno‐associated virus‐BI30 (AAV‐BI30) injected reduce expression the cerebrovascular endothelial cells (CVECs). The effects phenotypes and mice were examined through behavioral tests, two‐photon imaging, flow cytometry, Western blot, immunohistochemistry, quantitative polymerase chain reaction assay (qPCR). RESULTS increased CVECs of patients with AD. Overexpression primary enhanced Aβ generation regulating beta‐site APP cleaving enzyme 1 (BACE1) γ‐secretase. further expression, creating a vicious cycle. Knockdown decreased accumulation within walls, reduced Alzheimer's‐related pathology, improved cognitive performance transgenic mice. DISCUSSION alleviates pathology impairment. Targeting holds promise for treatment. Highlights ( ) (CVECs) Cerebrovascular regulates deposits improves impairments could be potential target treatment

Language: Английский

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Causal associations between major depressive disorder and COVID-19

General Psychiatry, Journal Year: 2023, Volume and Issue: 36(2), P. e101006 - e101006

Published: April 1, 2023

We aimed to evaluate whether major depressive disorder (MDD) could aggravate the outcomes of coronavirus disease 2019 (COVID-19) or genetic liability COVID-19 trigger MDD.We assess bidirectional causal associations between MDD and COVID-19.We performed correlation Mendelian randomisation (MR) analyses potential three outcomes. Literature-based network analysis was conducted construct molecular pathways connecting found that has positive correlations with (rg: 0.10-0.15). Our MR indicated is associated increased risks infection (odds ratio (OR)=1.05, 95% confidence interval (CI): 1.00 1.10, p=0.039). However, did not confer any effects on MDD. Pathway identified a panel immunity-related genes may mediate links COVID-19.Our study suggests increase susceptibility COVID-19. findings emphasise need social support improve mental health intervention networks for people mood disorders during pandemic.

Language: Английский

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Causal effects of COVID-19 on structural changes in specific brain regions: a Mendelian randomization study

BMC Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: July 19, 2023

Abstract Background Previous studies have found a correlation between coronavirus disease 2019 (COVID-19) and changes in brain structure cognitive function, but it remains unclear whether COVID-19 causes structural which specific regions are affected. Herein, we conducted Mendelian randomization (MR) study to investigate this causal relationship identify vulnerable COVID-19. Methods Genome-wide association (GWAS) data for phenotypes (28,900 cases 3,251,161 controls) were selected as exposures, GWAS traits (cortical thickness surface area from 51,665 participants volume of subcortical structures 30,717 participants) outcomes. Inverse-variance weighted method was used the main estimate method. The median, MR-Egger, MR-PRESSO global test, Cochran’s Q statistic detect heterogeneity pleiotropy. Results genetically predicted infection phenotype nominally associated with reduced cortical caudal middle frontal gyrus ( β = − 0.0044, p 0.0412). hospitalized lateral orbitofrontal 0.0049, 0.0328) rostral 0.0022, 0.0032) well temporal 10.8855, 0.0266). These relationships also identified severe phenotype. Additionally, cuneus 0.0024, 0.0168); pericalcarine 2.6628, 0.0492), superior parietal 5.6310, 0.0408), parahippocampal 0.1473, 0.0297); hippocampus 15.9130, 0.0024). Conclusions Our indicates suggestively significant genetic predisposition atrophy functional human brain. Patients impairment should be actively managed alleviate neurocognitive symptoms minimize long-term effects.

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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A phenome‐wide investigation of risk factors for severe COVID‐19

Journal of Medical Virology, Journal Year: 2022, Volume and Issue: 95(1)

Published: Nov. 1, 2022

With the continued spread of COVID-19 globally, it is crucial to identify potential risk or protective factors associated with COVID-19. Here, we performed genetic correlation analysis and Mendelian randomization examine relationships between hospitalization 405 health conditions lifestyle in 456 422 participants from UK Biobank. The revealed 134 positive 65 negative correlations, including those intakes a variety dietary components. MR indicates that set body fat-related traits, maternal smoking around birth, basal metabolic rate, lymphocyte count, peripheral enthesopathies allied syndromes, blood clots leg, arthropathy are causal for severe COVID-19, while higher education attainment, physical activity, asthma, never status protect against illness. Our findings have implications stratification patients prevention its outcomes.

Language: Английский

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Alzheimer’s disease and COVID-19: Interactions, intrinsic linkages, and the role of immunoinflammatory responses in this process

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 9, 2023

Alzheimer’s disease (AD) and COVID-19 share many common risk factors, such as advanced age, complications, APOE genotype, etc. Epidemiological studies have also confirmed the internal relationship between two diseases. For example, found that AD patients are more likely to suffer from COVID-19, after infection with has a much higher of death than other chronic diseases, what’s interesting is developing in future significantly COVID-19. Therefore, this review gives detailed introduction perspectives epidemiology, susceptibility mortality. At same time, we focused on important role inflammation immune responses promoting onset

Language: Английский

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Causal associations and genetic overlap between COVID-19 and intelligence

QJM, Journal Year: 2023, Volume and Issue: 116(9), P. 766 - 773

Published: June 7, 2023

COVID-19 might cause neuroinflammation in the brain, which could decrease neurocognitive function. We aimed to evaluate causal associations and genetic overlap between intelligence.We performed Mendelian randomization (MR) analyses assess potential three outcomes intelligence (N = 269 867). The COVID phenotypes included severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection 501 486), hospitalized 1 965 329) critical 743 167). Genome-wide risk genes were compared genome-wide association study (GWAS) datasets on intelligence. In addition, functional pathways constructed explore molecular connections intelligence.The MR indicated that liabilities SARS-CoV-2 (odds ratio [OR]: 0.965, 95% confidence interval [CI]: 0.939-0.993) (OR: 0.989, CI: 0.979-0.999) confer effects There was suggestive evidence supporting effect of 0.988, 0.972-1.003). Hospitalized share 10 within genomic loci, including MAPT WNT3. Enrichment analysis showed these are functionally connected distinct subnetworks 30 linked cognitive decline. pathway revealed COVID-19-driven pathological changes brain multiple peripheral systems may lead impairment.Our suggests exert a detrimental tau protein Wnt signaling mediate influence

Language: Английский

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Causal Associations between Posttraumatic Stress Disorder and COVID-19

Journal of Integrative Neuroscience, Journal Year: 2024, Volume and Issue: 23(4), P. 68 - 68

Published: April 1, 2024

Objective: We aimed to evaluate bidirectional genetic relationships between posttraumatic stress disorder (PTSD) and COVID-19. Methods: investigated potential causal associations PTSD two COVID-19 conditions (COVID-19 hospitalization SARS-CoV-2 infection) via Mendelian randomization (MR) analyses. Three genome-wide association study (GWAS) summary datasets were used in the study, including (N = 174,659), infection 2,597,856), 2,095,324). performed a literature-based analysis uncover molecular pathways connecting Results: found that exerts effect on (odds ratio (OR): 1.10, 95% confidence interval (CI): 1.00–1.21, p 0.048) hospitalized (OR: 1.34, CI: 1.07–1.67, 0.001). However, both not associated with risk of PTSD. Pathway revealed several immunity-related genes may link Conclusions: Our suggests was increased risks for susceptibility severity. Early diagnosis effective treatment individuals infected coronavirus improve management outcomes

Language: Английский

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Promising Strategies to Reduce the SARS-CoV-2 Amyloid Deposition in the Brain and Prevent COVID-19-Exacerbated Dementia and Alzheimer’s Disease

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(6), P. 788 - 788

Published: June 16, 2024

The COVID-19 pandemic, caused by infection with the SARS-CoV-2 virus, is associated cognitive impairment and Alzheimer’s disease (AD) progression. Once it enters brain, virus stimulates accumulation of amyloids in brain that are highly toxic to neural cells. These may trigger neurological symptoms COVID-19. meningeal lymphatic vessels (MLVs) play an important role removal toxins mediate viral drainage from brain. MLVs considered a promising target prevent COVID-19-exacerbated dementia. However, there limited methods for augmentation MLV function. This review highlights new discoveries field COVID-19-mediated amyloid development strategies stimulate clearance through other pathways. based on innovative treating dysfunction induced infection, including use photobiomodulation, plasmalogens, medicinal herbs, which offer hope addressing challenges posed virus.

Language: Английский

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Causal relationship of COVID-19 on Alzheimer’s disease: an updated Mendelian randomization study

Neurological Sciences, Journal Year: 2023, Volume and Issue: 44(8), P. 2643 - 2644

Published: April 15, 2023

Language: Английский

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