Do APOE4 and long COVID-19 increase the risk for neurodegenerative diseases in adverse environments and poverty?
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ABSTRACT:
SUBMITTER: Ciurleo GCV
PROVIDER: S-EPMC10483995 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
Publications
Do <i>APOE</i>4 and long COVID-19 increase the risk for neurodegenerative diseases in adverse environments and poverty?
Ciurleo Gabriella C V GCV Tavares-Júnior José Wagner Leonel JWL Vieira Carlos Meton A G CMAG Braga-Neto Pedro P Oriá Reinaldo B RB
Frontiers in neuroscience 20230824
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Project description:The pandemic of Coronavirus Disease 2019 (COVID-19) presents the world with the medical challenge associated with multifactorial nature of this pathology. Indeed COVID-19 affects several organs and systems and presents diversified clinical picture. COVID-19 affects the brain in many ways including direct infection of neural cells with SARS-CoV-2, severe systemic inflammation which floods the brain with pro-inflammatory agents thus damaging nervous cells, global brain ischaemia linked to a respiratory failure, thromboembolic strokes related to increased intravascular clotting and severe psychological stress. Often the COVID-19 is manifested by neurological and neuropsychiatric symptoms that include dizziness, disturbed sleep, cognitive deficits, delirium, hallucinations and depression. All these indicate the damage to the nervous tissue which may substantially increase the incidence of neurodegenerative diseases and promote dementia.
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Project description:This study investigates adverse events following vaccination in patients with four neurodegenerative diseases: Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease, Multiple Sclerosis (MS), and Parkinson's disease. We applied advanced data processing techniques to analyze symptom patterns and severity scores across these disease groups. Patients were identified through filtering, and symptom clusters were extracted to group similar symptoms into distinct clusters, and severity scores were computed based on hospitalization and death reports. A chi-squared test was performed to assess the statistical significance of adverse event distributions among the diseases for different vaccines. The results reveal that ALS patients exhibit severe respiratory symptoms post-vaccination, while Alzheimer's patients report significant respiratory and gastrointestinal issues. MS patients commonly experience general symptoms such as fatigue, while Parkinson's patients face exacerbated motor symptoms. Notably, our analysis showed no significant difference in adverse event reporting rates between COVID-19 and pneumococcal vaccines across these disease groups. This research provides new insights into disease-specific responses to vaccines, emphasizing the importance of personalized monitoring and treatment strategies to mitigate risks and improve clinical outcomes in these vulnerable populations.
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Project description:This SuperSeries is composed of the SubSeries listed below.
2017-09-19 | GSE101689 | GEO
Project description:Microglia play a pivotal role in the maintenance of brain homeostasis but lose homeostatic function during neurodegenerative disorders. We identified a specific apolipoprotein E (APOE)-dependent molecular signature in microglia from models of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Alzheimer's disease (AD) and in microglia surrounding neuritic β-amyloid (Aβ)-plaques in the brains of people with AD. The APOE pathway mediated a switch from a homeostatic to a neurodegenerative microglia phenotype after phagocytosis of apoptotic neurons. TREM2 (triggering receptor expressed on myeloid cells 2) induced APOE signaling, and targeting the TREM2-APOE pathway restored the homeostatic signature of microglia in ALS and AD mouse models and prevented neuronal loss in an acute model of neurodegeneration. APOE-mediated neurodegenerative microglia had lost their tolerogenic function. Our work identifies the TREM2-APOE pathway as a major regulator of microglial functional phenotype in neurodegenerative diseases and serves as a novel target that could aid in the restoration of homeostatic microglia.
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Project description:We performed single cell RNA-sequencing of lungs from APOE knock-in mice in the absence of infection or four days post infection with SARS-CoV-2 MA10. Infected mice showed major remodeling of the cellular composition with expansion of myeloid cells and relative depletion of epithelial cells. In infected mice, APOE2 mice showed enrichment of pathways implicated in immune activation, consistent with immunologic misfiring.
2022-08-07 | GSE199498 | GEO
Project description:Microglia play a pivotal role in the maintenance of brain homeostasis, but lose their homeostatic function during the course of neurodegenerative disorders. We identified a specific APOE-dependent molecular signature in microglia isolated from mouse models of amyotrophic lateral sclerosis, multiple sclerosis and Alzheimer’s disease (SOD1, EAE and APP-PS1) and in microglia surrounding neuritic A-plaques in human Alzheimer’s disease brain. This is mediated by a switch from a (M0)-homeostatic to (MGnD)-neurodegenerative phenotype following phagocytosis of apoptotic neurons via the TREM2-APOE pathway. TREM2 induces APOE signaling which is a negative regulator of the transcription program in M0-homeostatic microglia. Targeting the TREM2-APOE pathway restores the M0-homeostatic signature of microglia in APP-PS1 and SOD1 mice and prevents from neuronal loss in an acute model of neurodegeneration. In SOD1 mice, TREM2 regulates MGnD in a gender-dependent manner. APOE-mediated MGnD microglia lose their tolerogenic function. Taken together, our work identifies the TREM2-APOE pathway as a major regulator of microglial functional phenotype in neurodegenerative diseases and serves as a novel target to restore homeostatic microglia. MG550 custom-design Nanosting chips were used to identify disease-associated vs. homeostatic molecular microglia signature in microglia in different disease models and transgenic models.
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