Adult mental health, Alzheimer's, Dementia

Investigating the role of brain tissue proteins in Alzheimer’s disease

Cardiff Institute for Tissue Engineering and Repair (CITER) provides a number of bursaries to its members. One of these is the Undergraduate Summer Student Bursary. This is available to CITER members to support undergraduate students’ research projects. These take place over a maximum of eight weeks during the summer.

In 2017, CITER awarded six bursaries (£1520 per student). In this blog we hear from undergraduate student Melissa Thomas who undertook her eight week placement in the School of Pharmacy and Pharmaceutical Sciences, and her supervisor, Dr Emma Kidd.

Melissa Thomas

Alzheimer’s disease is the most common form of neurodegenerative disease, affecting millions of people worldwide. It is typically characterised by a progressive decline in cognitive function, with memory being particularly affected. There is no cure, and available treatments offer only mild relief from symptoms.

The lack of effective available treatments stems in part from an uncertainty regarding the pathological mechanisms underlying the condition. This uncertainty persists, despite intense research efforts worldwide.

During my CITER summer placement I investigated the expression of mitochondrial proteins in brain tissue from patients with Alzheimer’s disease.

Comparing human brain tissue from an ageing range of human male and female brains with brains from male and female Alzheimer’s disease patients was innovative. There is not much research which examines the inter-relationship between ageing and gender for the risk of developing Alzheimer’s disease. The aim of this research was to pursue the possibility of developing novel anti-oxidants for the treatment of neurodegenerative diseases.

From studies of post-mortem brain tissue, a loss of specialised brain cells, called neurones, is observed in the brains of those who suffered Alzheimer’s disease, in comparison with people who do not have the disease. Additionally, the brains of Alzheimer’s disease patients contain structures called neurofibrillary tangles made of the protein tau and have plaques due to the accumulation of a small protein, beta amyloid. It is known that the loss of neurones and the presence of tangles and plaques are central to disease pathology. Interestingly, recent studies have shown that mitochondria, the ‘batteries’ of cells, start to malfunction before plaques can be detected – suggesting that mitochondrial dysfunction may be a primary event in Alzheimer’s disease. Identifying the primary events occurring in the pathology of Alzheimer’s disease could potentially lead to the identification of novel therapeutic targets, and allow for earlier diagnosis.

This mitochondrial dysfunction may be attributed to altered levels of mitochondrial proteins associated with the electron transport chain which provides power for the cell. This was suggested by previous studies (Chandrasekaran et al., 1997Liang et al., 2008 ) demonstrating significant differences in the levels of genes encoding mitochondrial protein subunits in brain samples of those who suffered from Alzheimer’s disease, in comparison with healthy controls. The aim of my investigation was to evaluate the levels of mitochondrial protein subunits present in human brain tissue samples. The results were compared across disease status (Alzheimer’s disease vs healthy controls), gender and age, to see whether there were any significant differences in the levels of proteins recorded.

The methodology involved using frontal cortex samples from human brains with Western blotting where proteins are separated according to their size and then identified using specific antibodies. The antibody cocktail used here was specific for five subunits of different mitochondrial proteins: V-ATP5A, III-UQRC2, II-SDHB, IV-COX II, and I-NDUFB8.

Following optimisation, I found the antibody cocktail worked well. Figure 1 shows a representative Western blot, showing samples from neurologically healthy young, middle-aged, and old men.

Analysis of my results showed there was no significant difference in the levels of any of the mitochondrial protein subunits between any of the sample groups. This suggests there is no difference in the levels of mitochondrial proteins across disease status, gender, or age. There did, appear to be a trend for increased protein subunit levels in the frontal cortex of women with Alzheimer’s disease, compared with the samples from men. This will be investigated further.

I’d like to thank CITER for giving me the opportunity to complete this placement. I was able to expand on my laboratory skills, which increased my confidence massively. I have no doubt that this will benefit me as I hopefully enter postgraduate education. I would like to thank Dr Emma Kidd, Dr Emma Lane, Dr Hannah Scott, and Dr Tom Phillips for their excellent supervision. I would also like to thank Aws Radef for his contribution to the laboratory work.

Dr Emma Kidd

This bursary allowed us to obtain preliminary data on how the expression of mitochondrial electron transport chain proteins in the human brain is affected by age and gender; two of the most important risk factors for developing Alzheimer’s disease. These data are essential for an upcoming manuscript and we would not have been able to obtain them without the CITER funding for Melissa.

Undergraduate final year pharmacy students are continuing with Melissa’s work as part of their research projects. The data Melissa obtained are also being used as part of a future grant application.

 

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