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.
Mariana Martins1, Dhanush Sivasankaran1, Noé Quittot1
1Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
Summary
Altered Tau phosphorylation impacts its seeding activity in Alzheimer's disease (AD). Reducing Tau phosphorylation levels decreases its ability to aggregate and propagate, offering potential therapeutic targets for AD.
Area of Science:
- Neuroscience
- Biochemistry
- Molecular Biology
Background:
- Tau protein aggregation and propagation are key features of Alzheimer's disease (AD) pathogenesis.
- Aggregated Tau seeds template normal Tau aggregation in a prion-like manner, correlating with disease progression.
- The specific molecular drivers and phosphorylation-dependent mechanisms of Tau seeding remain incompletely understood.
Purpose of the Study:
- To investigate how Tau's phosphorylation profile influences its seeding propensity in Alzheimer's disease.
- To determine the impact of specific phosphorylation sites on Tau's seeding competency.
Main Methods:
- Extraction and fractionation of Tau species from AD human brain tissue using size-exclusion and anion-exchange chromatography.
- Partial dephosphorylation of Tau species using lambda protein phosphatase.
- Characterization of Tau phosphorylation profiles via mass spectrometry and anti-Tau phospho-site antibodies.
- Assessment of Tau seeding activity using Förster resonance energy transfer (FRET)-based biosensor cells.
Main Results:
- Lambda protein phosphatase treatment modulated Tau phosphorylation levels.
- Mass spectrometry and biochemical techniques systematically characterized the phosphorylation profiles of Tau species.
- Reduced phosphorylation levels of Tau species correlated with decreased seeding activity in FRET-based biosensor cells.
Conclusions:
- Tau post-translational modifications, specifically phosphorylation, are intricately linked to its seeding activity.
- Modulating Tau phosphorylation presents a potential therapeutic strategy to inhibit Tau seeding and propagation in Alzheimer's disease.
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