Dr Lindsey Sinclair, Clinical Research Fellow at the University of Bristol Medical School, used data from two large US Alzheimer’s Disease cohorts – the Alzheimer’s Disease Neuroimaging initiative, and the National Alzheimer’s Coordinating Centre – to identify areas of brain atrophy, and the Brains for Dementia Research cohort in the UK to examine clinical differences in depression and dementia.
Genes and sequencing
“I also used polygenic risk scores for depression (which look at whether the depression is caused by two or more genes) to examine whether people at higher genetic risk of depression are more likely to develop depression during Alzheimer’s Disease,” continued Dr Sinclair. “Finally, I used microarray and RNA sequencing techniques from human post-mortem brain tissue from patients with Alzheimer’s disease who also suffered from depression, using tissue from UK based brain banks and data from the ROSMAP (Religious Orders Study/Memory and Ageing Project) study.”
ROSMAP
ROSMAP is a long-term initiative investigating memory, motor and functional problems in older Catholic nuns, priests and brothers across the United States of America. Dr Sinclair measured differences in gene expression in those with depression in Alzheimer’s Disease, which allows the identification of pathways potentially involved in the development of depression in Alzheimer’s disease which can be subject to further scrutiny.
Publications are key
Dr Sinclair has had two papers published on this work, in the Journal of Alzheimer’s Disease Reports and the International Journal of Geriatric Psychiatry. A further 5 are either in preparation or currently under review. However, due to COVID-19 and its ensuing complications – from lockdown, through collaborative institutional delays, and the complications of orchestrating work and families, Dr Sinclair’s work became much more challenging.
“My fellowship, which was due to end in June 2023, was delayed thanks to Covid, and Covid related lab closures. When factored in with childcare which was disrupted by Covid and a new baby, I needed some help in order to finish the labwork and produce the publications necessary to further my career and apply for a Senior Research Fellow position.”
A little support
So Dr Sinclair applied for funds from the COVID-19 support scheme for early career researchers from the Elizabeth Blackwell Institute.
“The funding from the Elizabeth Blackwell Institute saved my career, I think!” said Dr Sinclair. “I could finish off any outstanding work, write numerous publications and I applied for senior fellowships with a much greater chance of success. As a result of the funding I have extended my network of collaborators and I feel that I am in the perfect position to now transition to research independence.”
Onwards and upwards
Dr Sinclair has since been awarded an Alzheimer’s Research UK pilot grant to study microglial gene expression in depression in Alzheimer’s disease, in addition to the neuronal gene expression that she had already planned to study, and she has submitted the first two of her applications for senior research fellowships.
She was recently awarded a New Investigator award by the American Alzheimer’s Association Neuropsychiatric Symptoms professional interest area group and the Hannah Steinberg Award by the British Association of Psychopharmacology.
“I have also recently obtained funding from the James Tudor Foundation and the alumni office to appoint my first PhD student,” Dr Sinclair continued. “I am co-supervising with Professor Pat Kehoe and colleagues from Cardiff University. The PhD is titled, “The relationship of psychological symptoms in dementias to genetic risk”. This would also not have been possible without the support of the Elizabeth Blackwell Institute.”