gms | German Medical Science

Background: The epigenome exerts essential influence on regulation of cellular proliferation and differentiation. One of the most important fields in epigenome research is the investigation of DNA methylation. It is known that a 5-methylation of cytosine by DNA-methyltransferases within the promoter region of genes leads to a subsequent inactivation of transcription.

Question: Alzheimer’s disease (AD) represents the most common form of neurodegenerative disorders. Despite intensive research, the pathological processes leading to AD remain unknown. Thereby, genetic mutations can be found only in a minority of AD cases, in more than 90 % of cases there are no mutations detectable. Thus, the question arises if there is a significant contribution of the epigenome to AD pathogenesis and if AD related changes can also be found during physiological ageing.

Methods: As the epigenome is cell type specific, epigenomic studies require the investigation of the target tissue. Since the brain consists of a mixture of numerous different cell types, conscious epigenomic studies require the isolation of distinct cell types. Here, we isolated highly pure neurons and glia from human brain samples and performed genome-wide methylation analysis during progression of AD. Furthermore we performed an integrated analysis of AD related changes and changes occurring during physiological ageing.

Results: Interestingly we found severe cell type specific changes of the methylation patterns of neurons and glia emphasizing the need to separate cell types for epigenomic studies. Furthermore, we found distinct, cell type specific methylation changes in AD brains compared with “healthy” controls.

Conclusions: We demonstrated the need to separate distinct cell types in the context of brain epigenomics. Our integrated analysis showed that the progression of AD correlates with distinct, cell type specific changes of the methylation landscape.