Neurodegeneration and Dementia
One of the core research themes within the Complex Disease Epigenetics group is in the area of Neurodegeneration and dementia, which is lead by Dr Katie Lunnon. We are currently funded by the Alzheimer’s Association, the Medical Research Council, the Alzheimer’s Society, Alzheimer’s Research UK and other international funders to perform epigenomic studies in dementia. We currently hold more than £1.7million in funding for a range of dementia focussed projects, being undertaken by five postdoctoral research fellows and nine PhD students.
The main focus of our work is on Alzheimer’s disease (AD), which is a chronic neurodegenerative disorder that is characterized by progressive neuropathology and cognitive decline and accounts for 60-80% of dementia cases. We recently published the first epigenome-wide association studies (EWAS) in AD [Lunnon et al., 2014 ; [De Jager et al., 2014 ] using the Illumina 450K array. We performed a cross-tissue analysis of methylomic variation in AD using samples from multiple human post-mortem brain cohorts. Of particular interest we identified a differentially methylated region in the ankyrin 1 (ANK1) gene that was associated with neuropathology in the entorhinal cortex, a primary site of AD manifestation. This region was confirmed as being substantially hypermethylated in two other cortical regions (superior temporal gyrus and prefrontal cortex), but not in the cerebellum, a region largely protected from neurodegeneration in AD, or whole blood obtained pre-mortem from the same individuals. Neuropathology-associated ANK1 hypermethylation was subsequently confirmed in cortical samples from other independent brain cohorts.
More recently we have built upon these previous findings to characterise ANK1 in the brain to establish its functional role in neuropathology. In addition to looking beyond DNA methylation and exploring the role of DNA hydroxymethylation and various histone modifications in AD brain. Finally, in collaboration with other groups across the world, we are combining clinical, genetic and multi-omic data (GWAS, EWAS and transcriptomic data) in several thousand cases to undertake the first integrated meta-analysis of AD. A selected list of currently funded projects in the group can be found below: