The role of proteomics in dementia and Alzheimer's disease.

Proteomic analysis enables us to identify dementia-related protein profiles of both genetic and environmental origins. In this review, current proteomics technologies are described including many examples of clinical proteomics studies. Many of these studies present only results of the discovery phase. Progression to the validation phase was achieved by developing more advanced proteomics technologies such as fluorescence two-dimensional differential gel electrophoresis or isobaric tagging for relative and absolute protein quantification. These technologies will lead to the design of several new Alzheimer's disease-related protein panels for the analysis of CSF. On these new panels, established markers such as tau and Abeta42 will be used in combination with novel markers, for example beta-2-microglobulin, brain-derived neurotrophic factor 1 and fragments of cystatin C. However, there are still limitations to using proteomic assays. The preparation of homogeneous sample material is difficult due the complexity of brain tissue. Laser capture microdissection and recently developed more sensitive proteomics methods, for example fluorescence saturation labelling, will overcome these limitations. Combining proteomics with approaches at the level of the genome and transcriptome followed by interpretation by systems biology will soon shed further light on dementia-related pathogenesis.