Neuroinflammation, sleep and dementia: strategies to reduce symptoms and disease progression

Neuroinflammation driven by microglial cells is a key cellular hallmark of dementia. Neuroinflammation correlates with tau pathology and predicts cognitive decline and the severity of Alzheimer’s disease. Sleep disturbances are a modifiable risk factor for Alzheimer’s disease and strategies to improve sleep are promising interventions. In humans, REM sleep is a significant risk factor for dementia. However, the role of REM sleep in dementia is unknown and a better understanding of the cellular mechanisms linking sleep, brain function, neuroinflammation and other hallmarks of disease is required to develop effective treatments for dementia.

This project will further characterise the impact of REM sleep on neuroinflammation in older human participants who are either cognitively intact or have mild cognitive impairment and dementia. Sleep structure (NREM and REM sleep), sleep disorders (e.g. sleep apnoea), EEG and cognitive assessments will be undertaken. Blood based biomarkers for neuroinflammation, neurodegeneration and peripheral inflammation will be investigated using biochemical techniques and state-of-the-art approaches, such as RNA sequencing and proteomics, to provide a comprehensive characterisation of the effects of sleep on cellular aspects associated with neuroinflammation.

The PhD candidate will be based at the Surrey Sleep Research Centre and the Section of Immunology within the Faculty of Health and Medical Sciences (FHMS) under the supervision of Prof Derk-Jan Dijk and Dr Natalie Riddell. The candidate will benefit from an extensive training in integrative physiology, immunology, and neuroscience focusing on Alzheimer’s disease and other dementia syndromes.

• Applicants are expected to hold a good honours degree (upper second) in an appropriate discipline
• Have a IELTS test score (6.5 or above overall and at least 6 in each category) if English is not your first language
• Available for UK students. 

Prof Derk-Jan Dijk is a Professor of Sleep and Physiology, Director of the Surrey Sleep Research and Group Leader in the UK-Dementia Research Institute (DRI). His research focuses on sleep and circadian rhythms in humans and how these are affected by ageing, light, hypnotics, and other factors. He also studies the effects of insufficient sleep and circadian disruption on the transcriptome and found major effects of these manipulations on transcripts related to immune function. A current research focus is sleep and dementia and the development and validation of technologies to monitor and improve sleep and circadian disturbance in dementia. This research is conducted in both the homes of the research participants as well as in the recently created UK-DRI Living Lab Clinical Research Facility at the University of Surrey. This facility enables intensive physiological monitoring (e.g. polysomnography, blood sampling) to be conducted in people living with dementia in an environment which combines aspects of ‘the home’ and a clinical research lab. Derk-Jan has a track record in multidisciplinary research funded by BBSR, AFOSR, MRC/UK DRI and industry.     

Dr Natalie Riddell is a Lecturer in Immunology and Ageing. Her research is focused on the effect of neuro-endocrine regulation on immune function and how this interacts with immune ageing. Her main research findings include the increased responsiveness of senescent T cells to sympathetic nervous system activation and a greater understanding of how senescence cells accumulate in-vivo, reasons for their reduced cellular functions, and identification of signalling pathways involved in maintaining cellular senescence. A current research focus is the impact of circadian rhythms and seasonal effects on immunity across the life course. Natalie’s work has been on human immunology including analysis of ex-vivo primary cells with or without in-vivo psychological (e.g. laboratory stress test), physical (e.g. exercise), pharmacological, nutritional, and time-of-day and year manipulations. Natalie supervises several doctoral, MSci and placements year students and technicians undertaking multiple research project. Her research has been funded by the BBSRC, Dunhill Medical Trust, NIH, and FHMS at the University of Surrey.  

References:

Raphaelle Winsky-Sommerer, Paula de Oliveira, Sally Loomis, Keith Wafford, Derk-Jan Dijk , Gary Gilmour. Disturbances of sleep quality, timing and structure and their relationship with other neuropsychiatric symptoms in Alzheimer's disease and schizophrenia: Insights from studies in patient populations and animal models. Neurosci Biobehav Rev. 2019 Feb;97:112-137.

Michael R Irwin, Michael V Vitiello. Implications of sleep disturbance and inflammation for Alzheimer's disease dementia. Lancet Neurol. 2019 Mar;18(3):296-306.

Section and Facilities links:

https://ukdri.ac.uk/team/derk-jan-dijk

https://www.surrey.ac.uk/school-biosciences-medicine/research/section-sleep

https://www.surrey.ac.uk/school-biosciences-medicine/research/section-immunology

https://crc.surrey.ac.uk/

https://www.surrey.ac.uk/school-biosciences-medicine/facilities/bioimaging-and-flow-cytometry