The role of galectin-3 in regulating microglia inflammation in Alzheimer’s disease
(2017) MOBT01 20162Degree Projects in Molecular Biology
- Popular Abstract
- Brain Inflammation in Alzheimer’s disease
Nowadays, Alzheimer’s disease (AD) is the main cause of dementia worldwide but still is not well understood how is the disease developed. However, there are few known factors that are important in the progression of the disease. In the last decade, the role of the inflammatory cells has been clearly link to the pathology. Hence, the aim of our project is to find a relationship between the immune cells of the brain, called microglia, and AD in both mice and human brains.
During the course of the disease two important proteins, called beta-amyloid and tau, build up structures called plaques and tangles, respectively. These structures lead to neuronal malfunction, which in time induce the death... (More) - Brain Inflammation in Alzheimer’s disease
Nowadays, Alzheimer’s disease (AD) is the main cause of dementia worldwide but still is not well understood how is the disease developed. However, there are few known factors that are important in the progression of the disease. In the last decade, the role of the inflammatory cells has been clearly link to the pathology. Hence, the aim of our project is to find a relationship between the immune cells of the brain, called microglia, and AD in both mice and human brains.
During the course of the disease two important proteins, called beta-amyloid and tau, build up structures called plaques and tangles, respectively. These structures lead to neuronal malfunction, which in time induce the death of nerve cells in the brain. Brain’s immune cells, called glial cells, conforming the “army” of the brain that protects and maintain the homeostasis of the tissue. Microglial cells are considered the main cell type involved in the brain inflammation, and can either support the brain, i.e. “good” inflammatory response or be of a more destructive nature, referred to as the “bad” inflammatory response. The balance between both inflammatory responses elicited by microglial cells contributes to the healthy function of the brain.
The first part of this project was design to find how inflammation in the brain correlates with the disease progression in AD mice. We used a mouse model of AD, called 5xFAD, in which we confirmed the presence of the disease, in terms of plaques, already at 10 weeks of age. To study the disease progression, we used different methods to quantify proteins related to plaque development and the disease progression in mice at different age. We measured the most relevant proteins related to the pathology, amyloid beta and its precursor, the amyloid precursor protein (APP). Both, amyloid beta and APP were significantly upregulated over the progression of the disease in our mice. Next, we evaluated if the microglial cells in the brain were already responding to the disease. To that aim, we did evaluate different inflammatory factors. We found an altered inflammatory pattern compared to the mice not affected by the pathology. Then, we isolated the microglial cells from the mouse brain to analyze the protein signature in these cells in order to find any relationship between inflammation and microglia. The results showed that 5xFAD mice had an on-going inflammation in the brain before the first plaque deposition linking microglia to the progression of the disease.
In the human part of this project, we wanted to evaluate what kind of microglial cells are present in a human brain suffering from AD by studying brain sections from AD patients by immunohistochemistry. Microglial cells can be found in a “resting” state or activated state in the human brain. We wanted to know if a molecule involved in the microglial activation called galectin-3 (gal3) was present in the brain tissue from AD patients. Indeed, we found gal3 levels to be 10 times higher in brain from AD patients compared to healthy age-matched individuals. Notably, we found gal3 only in microglial cells associated with the amyloid plaques. Later, we analysed the plaques and found differences in shape and area between plaque with and without gal3. Those plaques containing gal3 have more irregular shape and a bigger area. Our results of the human data show a strong relationship between gal3 and inflammation in human AD patients.
Master’s Degree Project in Molecular Biology 60 credits 2017
Department of Biology, Lund University
Advisors: Tomas Deierborg and Antonio Boza Serrano
Experimental Neuroinflammation Lab /Faculty of Medicine, Lund University (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/8925250
- author
- Paulus, Agnes Agnieszka
- supervisor
- organization
- course
- MOBT01 20162
- year
- 2017
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 8925250
- date added to LUP
- 2017-09-11 11:13:29
- date last changed
- 2017-09-11 11:13:29
@misc{8925250,
author = {{Paulus, Agnes Agnieszka}},
language = {{eng}},
note = {{Student Paper}},
title = {{The role of galectin-3 in regulating microglia inflammation in Alzheimer’s disease}},
year = {{2017}},
}