Undergraduate bursaries 2015: Summary of projects
Imaging the degeneration of long-range axons in tauopathy
Principal Investigator: Dr Michael Ashby
Undergraduate student: Hester Bowers
Institution: University of Bristol
This project studied the effects of the Alzheimer's hallmark tau protein on brain cells. They used a fluorescent dye to study the structures of cells in the brains of mice that showed some symptoms of Alzheimer's disease. They found that some cells did show signs of damage, swelling up or disintegrating. Other brain cells nearby were unaffected. They suggest that this is explained by looking at the way tau usually functions in healthy cells. Tau is important in maintaining the structure and shape of the cells and in transporting cell components and molecules from one part of the cell to another. This leads to the theory that larger brain cells would be more susceptible to damage than smaller brain cells. Although this project does not provide direct support for this idea, it does suggest that different brain cells are affected differently by abnormal tau. The findings from this study can be used to design future experiments, particularly those exploring damage to brain cells caused by abnormal tau protein in mice.
Investigating homocysteic acid as a potential neurotoxin in Alzheimer's Disease
Principal Investigator: Dr Gayle Doherty
Undergraduate student: Amelia Hunter
Institution: St Andrews University
This project built on a previous finding that homocysteine, a naturally occurring chemical found in our blood, has a higher concentration in the blood of people living with Alzheimer's. It was also found that elevated homocysteine levels were associated with higher risk of Alzheimer's. As yet, how this homocysteine may affect Alzheimer's risk is unknown.
This study used several different experiments to shed light on what the mechanistic link may be between homocysteine and AD risk. Amelia's experiments focused on homocysteic acid (HA), a compound that is made from homocysteine, which has also been found to be elevated in people affected by Alzheimer's. The experiments involved exposing brain cells to a high concentration of homocysteic acid and studying the effects. They found that higher levels of homocysteic acid increased the concentrations of a substance that leads to oxidative stress, a process that is thought to contribute towards Alzheimer's progression, by damaging brain cells. They also found that high levels of homocysteic acid damaged the part of the cell that generates energy. This sort of damage leads to cell death and is associated with early stages of Alzheimer's disease. Amelia also demonstrated that the pathway by which homocysteic acid may cause these effects could involve a component of the membrane of cells. When cells were treated with both homocysteic acid and with a drug that blocked this membrane component, there were decreased levels of oxidative stress, and less damage to the energy generating part of the cell.
This result indicates that the role of homocysteic acid in brain cell damage merits further research. It also suggests the mechanism through which homocysteic acid damages cells, and points towards potential drug targets.
Amyloid beta modulation of calcium signalling in pericytes
Principal Investigator: Dr Mark Dallas
Undergraduate student: Sonia Chukwuka
Institution: University of Reading
There is a layer of cells between the brain and the blood, known as the 'blood-brain barrier', that regulate which molecules in the blood the brain is exposed to. This barrier prevents substances that are toxic to brain cells from getting from the blood into the brain and vice versa. It is thought that this barrier is deteriorated in the brains of people living with Alzheimer's, and the resulting exposure to the toxic molecules from the blood plays a role in brain cell damage associated with the disease. The cause of this deterioration is unknown. This study investigated two possibilities. Firstly, build-up of amyloid protein, an important part of the Alzheimer's disease process, has been suggested to cause deterioration of this barrier. To test this theory, the student treated cells from this barrier with amyloid protein. The amyloid did not damage these cells, suggesting that this theory may not be true. Secondly, it has been observed that there is an increase in the concentration of carbon monoxide in people with Alzheimer's, and it was thought that this carbon monoxide may contribute to deterioration of the blood-brain barrier. The student treated the barrier cells with carbon monoxide and observed chemical changes in the cells that indicated their function may be altered by the presence of carbon monoxide. The results from these experiments will inform more research into how the blood-brain barrier may be deteriorated in Alzheimer's. It may also indicate carbon monoxide as a potential drug target, particularly for early stages of Alzheimer's.
Signature blood amino acids in patients with mild cognitive impairment compared with Alzheimer's Disease
Principal Investigator: Professor Myra Conway
Undergraduate student: Miriam Bourne
Institution: University of the West of England
This study investigated a potential avenue for diagnosis of Alzheimer's and mild cognitive impairment from blood samples. There is some evidence that suggests people with Alzheimer's and people with mild cognitive impairment may have altered amounts of a group of molecules called amino acids in their blood and brain. Miriam used blood samples donated by a small group of people with mild Alzheimer's or mild cognitive impairment, testing the samples for the concentrations of several different amino acids. She found that there was a difference in the levels of an amino acid called glutamate between people without dementia or cognitive decline, people with Alzheimer's, and people with mild cognitive impairment. Other amino acids may also have altered levels. Further study with more participants is needed to support this result more strongly. This would also indicate if changes in amino acids were a good way to diagnose Alzheimer's or cognitive impairment, and whether they may possible be a target for treatments.