Neuroplastin is a highly glycosylated transmembrane protein whose membrane positioning is dependent on membrane ganglioside composition. In this thesis, we investigated changes of neuroplastin expression in neurodegeneration. In human hippocampal tissue affected by sporadic Alzheimer's disease (AD), we show that neuroplastin immunoreactivity pattern is similar to control pattern, namely in cell bodies and dendrites of glutamatergic neurons of the trisynaptic pathway. Neuroplastin immunoreactivity is highly increased in AD, particularly in the dentate gyrus and subiculum in early stages of the disease. In a transgenic mouse model of familial AD, neuroplastin and plasma membrane calcium ATP-ase expression are decreased in cortex and hippocampus when compared to wild-type mice. This finding may be attributed to changed molecular mechanisms of learning and memory disorder. Neuroplastin expression and its positioning within membrane domains is highly dependent on ganglioside composition and thus directly affected when membrane ganglioside composition is altered, as shown by analysis of isolated membrane fractions derived from brain tissue of different mice models with aberrant ganglioside synthesis. In vitro studies showed that GM1, a complex a-series ganglioside, predominantly co-localizes with neuroplastin and is probably responsible for its positioning within lipid rafts. Based on joined data of already described alterations of membrane domains in neurodegeneration and here presented association of expression and membrane positioning of neuroplastin with ganglioside composition, we conclude that neuropathological cascade in Alzheimer’s disease affects cell-adhesion molecule neuroplastin. Changed neuroplastin expression leads to altered cell calcium signaling and inability to maintain learning and memory molecular mechanisms.