Soluble oligomeric forms of amyloid beta (Aβ) play an important role in causing the cognitive deficits in Alzheimer's disease (AD) by targeting and disrupting synaptic pathways. Thus, the present research is directed toward identifying the neuronal pathways targeted by soluble forms and, accordingly, develops alternative therapeutic strategies. The neurotrophin brain-derived neurotrophic factor (BDNF) is synthesized as a precursor (pro-BDNF) which is cleaved extracellularly by plasmin to release the mature form. The conversion from pro-BDNF to BDNF is an important process that regulates neuronal activity and memory processes. Plasmin-dependent maturation of BDNF in the brain is regulated by plasminogen activator inhibitor-1 (PAI-1), the natural inhibitor of tissue-type plasminogen activator (tPA). Therefore, tPA/PAI-1 system represents an important regulator of extracellular BDNF/pro-BDNF ratio. In this review, we summarize the data on the components of the plasminogen activation system and on BDNF in AD. Moreover, we will hypothesize a possible pathogenic mechanism caused by soluble Aβ forms based on the effects on tPA/PAI-1 system and on the consequence of an altered conversion from pro-BDNF to the mature BDNF in the brain of AD patients. Translation into clinic may include a better characterization of the disease stage and future direction on therapeutic targets.

Department of Medical Chemistry and Clinical Biochemistry 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

International Clinical Research Centre St Anne's University Hospital Brno Czech Republic

Memory Clinic Department of Neurology 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

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