Biomarkers are objectively measurable parameters for accurate disease diagnosis and prognosis. For many diseases, like Alzheimers disease (AD), there is an urgent need for sensitive and specific biomarkers. Blood platelets are useful diagnostic targets and a promising “reservoir” for biomarkers. Compared to other body fluids and cell-types, they have several advantages, which are described, demonstrated and discussed in this work. The present thesis comprises of three proteomic publications that underpin the aptitude of platelets as a potent protein biomarker-source. Using two dimensional difference gel electrophoresis (2-D DIGE), firstly, “low biological- variation proteins” (LBVPs) are characterised. Those proteins are stably expressed under various circumstances and not affected by age, gender or specific diseases. Thus, they can be used as normalisation proteins and are applicable for accurate biomarker quantification. In this study we identified 14-3-3 gamma as a novel and optimal reference protein and re-evaluated the traditional reference proteins actin, tubulin and glyceraldehyde-3-phospate dehydrogenase. Besides LBVPs, highly variable proteins were investigated in publication #2. Most of them turned out to be high abundant plasma proteins, specifically taken up by platelets. However, for cytosolic proteins like glutathione S-transferase omega-1 (GSTO1), single nucleotide polymorphisms were identified as major cause for high variability of single spot abundances, while the sum of all GSTO1 spots was quite stably expressed in study individuals. Accordingly, in publication #2 we show that also genetic aspects have to be considered in proteomic biomarker discovery studies. They are important to classify the origin of high variable proteins. Finally, publication #3 is itself a biomarker - study in which we identify monoamine oxidase B (Mao-B) by 2-D DIGE as peripheral candidate biomarker, which was specifically increased in AD patients, but not in patients suffering from Parkinsons disease. In summary, in this doctoral thesis the causes as well as consequences of biological variation in biomarker studies are thoroughly,investigated . The results are a valuable contribution in this field and should foster the identification of reliable molecular markers.