Research - Neurodegeneration
There is a strong and multi-faceted neurodegeneration interest group in the University of Nottingham which has well established ties with clinical neurology. Recent achievements and ongoing work include:
- Novel mouse model for Lewy Body Disease. Professor Mayers team have carried out conditional gene ablation of a proteasomal regulatory ATPase in the substantia nigra using the loxP/Cre recombinase homologous recombination approach. This has recapitulated the neuropathology and neurochemical deficits of Parkinson's disease including loss of tyrosine hydroxylase positive neuronal projections to the basal ganglia. A new genetic model of Parkinson's disease has been created and moreover it has been demonstrated genetically that abolition of the 26S proteasome in neurones in the substantia nigra causes neuronal death and recapitulates the disease.
- Development of Ultra-High Field MRI diagnostic imaging of parkinsonian disorders at 3 and 7 Tesla. This work has built on the ward for a Nobel prize in the development of MRI to Sir Peter Mansfield of NottinghamUniversity. The ultra-high field programme is supported by grants from MRC and the Wellcome Trust, UK. The MRI Parkinsons Team includes: Professor Peter Morris, Dorothee Auer, Penny Gowland, Stephen Jackson and Dr Nin Bajaj and Matthew Brookes. A project due to be launched in 2010 will use a variety of MRI techniques, and the new techniques of transcranial ultrasound and magentoencephalography to further explore the pathogenic aetiology of tremor in parkinsonian conditions.
- Use of FP-CIT phenotyping in the evaluation of dystonic SWEDDs (Scans without evidence of dopaminergic deficiency). Industry grants from GE Electric (Bajaj) have allowed the detailed phenotyping of cohorts of patients with dystonic tremor mimicking Parkinsons disease. Future work will look at genetic loci that might pre-dispose to this condition and imaging work will evaluate the nature of the parkinsonian deficits in dystonic tremor. This in turn may give leads on new drug development.
- High field (7T) studies, led by Professor Auer, are planned in Alzheimer dementia including studies on iron deposition in amyloid cortical plaques.
- The Nottingham team (Mayer, Lowe andLennox) helped pioneer the use of anti-ubiquitin antibodies in the description of brain neurodegenerative diseases including Diffuse Lewy body diseases back in the late 1980s.
- We have recently been awarded >£2M in grants in the fields of Alzheimer Dementia (AD) and Parkinson's Disease (PD):
- PROBAND- Tracking Parkinson's Disease. Principal Applicant Dr Donald Grosset, University of Glasgow; Co-applicant Dr Nin Bajaj. £1.63M. Parkinson's UK. This will form the largest UK observational study in PD recruiting 2000 patients and 1000 controls over a 5 year period starting in Feb 2012. The trial will correlate genotype, ethnicity, MRI imaging findings and drug response with patient clinical phenotype.
- Ultra-sensitive, high throughput detection of molecular markers in blood for diagnosis of Alzheimer dementia. MRC DPFS grant. £650K. Principal Applicant, Professor Paul O'Shea, Nottingham University; Co-applicant Dr Nin Bajaj. Recruits April 2012 to Summer 2013. This trial will develop a new point of care diagnostic instrument using surface Plasmon resonance with our own in-house biomarker array for the serological diagnosis of AD.