Related Experiment Video
Updated: Jan 8, 2026
09:07
Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses
Published on: June 14, 2020
11.5K
Basic Science and Pathogenesis.
1Columbia University, New York, NY, USA; Taub Institute, New York, NY, USA.
Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
Summary
LINE-1 activation in microglia contributes to neuroinflammation and dysfunction in late-onset Alzheimer's disease (LOAD). This study identifies LINE-1 as a key factor in microglial impairment and a potential therapeutic target for Alzheimer's disease.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Microglia are crucial immune cells in the brain, implicated in late-onset Alzheimer's disease (LOAD) pathogenesis.
- Transposable elements, specifically long interspersed nuclear element-1 (LINE-1), are suspected contributors to neuroinflammation in LOAD.
- The precise role of LINE-1 in microglial dysfunction and its impact on Alzheimer's disease progression are not well understood.
Purpose of the Study:
- To investigate the role of LINE-1 expression and activation in microglial dysfunction within the context of LOAD.
- To determine if LINE-1 activation directly impacts microglial function, including morphology, phagocytosis, and inflammatory responses.
- To identify LINE-1 as a potential therapeutic target for LOAD.
Main Methods:
- Examined LINE-1-encoded open reading frame 1 protein (ORF1p) in postmortem brain tissue from LOAD patients and controls.
- Quantified ORF1p in microglia and correlated it with disease-associated morphology.
- Utilized human induced pluripotent stem cell-derived microglia (iMG) to model LINE-1 activation using CRISPR technology.
- Assessed microglial morphology, cytokine secretion, amyloid-beta (Aβ) phagocytosis, and transcriptomic changes in response to LINE-1 activation.
Main Results:
- Elevated ORF1p levels were found in microglia of LOAD patients, correlating with altered microglial morphology.
- Experimental LINE-1 activation in iMG led to morphological changes, increased pro-inflammatory cytokine secretion, and impaired Aβ phagocytosis.
- Transcriptomic analysis revealed that LINE-1 activation modulated genes involved in antigen presentation, lipid metabolism, and AD-related pathways.
Conclusions:
- LINE-1 activation is a significant driver of microglial dysregulation, exacerbating neuroinflammation and cellular dysfunction in LOAD.
- This research highlights LINE-1 as a novel mechanism underlying microglial impairment in Alzheimer's disease.
- LINE-1 presents a promising therapeutic target for modulating neuroinflammation and potentially treating LOAD.
Related Concept Videos
01:20Infection
11.6K
When a pathogen enters the body and reproduces, it can cause an infection, damage body cells, and cause illness symptoms that eventually lead to disease. Therefore, its prevention requires breaking the chain of infection.
The chain begins with pathogens: bacteria, viruses, fungi, prions, or parasites such as protozoa helminths. These can be present on the skin as transient or resident flora, or they can be acquired from the environment. Identifying and treating the type of infection and...
The chain begins with pathogens: bacteria, viruses, fungi, prions, or parasites such as protozoa helminths. These can be present on the skin as transient or resident flora, or they can be acquired from the environment. Identifying and treating the type of infection and...
11.6K
01:25Urinary Tract Infection II: Pathophysiology
524
The pathophysiology of urinary tract infections (UTIs) encompasses several progressive stages, beginning with bacterial colonization and culminating in potential systemic complications if untreated. UTIs are primarily initiated by bacteria, such as Escherichia coli, which often originate from the gastrointestinal tract and migrate to the urinary system through the periurethral area. This migration can occur via several routes, including improper hygiene practices, sexual activity, or...
524
01:23Cystic Fibrosis: Pathogenesis
676
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
676
01:29Pneumonia II: Pathophysiology
2.5K
The pathophysiology of pneumonia involves the following steps:
2.5K
01:26Stages of Infection
64.7K
Stages of infection describe what happens to a susceptible host once a pathogen invades the human body. The stages of infection are incubation, prodromal, illness, stage of decline, and convalescence. The incubation stage is the period from exposure to a pathogen until symptoms start. The infected person is unaware of impending illness as the pathogens grow and multiply within the body. The duration may vary depending on the type of infection. The incubation period of measles averages ten to...
64.7K
01:31Defense Against Bacterial Pathogens
2.6K
The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
2.6K