Synthesis and testing of fluorescent chemical compounds as diagnostic tools for Alzheimer's disease

Abstract

The most common neurodegenerative disease that causes dementia in humans is Alzheimer’s disease. This degeneration of neurons and synapses in the cerebral cortex is characterized by the loss of memory and other very important human skills like reasoning, abstraction and language. Nowadays, around 30 million people are affected by this disease. Histologically, Alzheimer’s disease is characterized by the presence of two microscopic lesions: extracellular senile (amyloid) plaques and neurofibrillary tangles. The senile plaques, also known as neuritic plaques, are made of deposits of amyloid beta peptide (ABeta), which derives from beta amyloid precursor protein (APP) by consecutive proteolytic cleavages. In a previous study, four chemical compounds were found to act as inhibitors of the in vitro and in vivo aggregation of ABeta peptide. In order to develop novel inhibitors that, furthermore, are capable of being used as diagnostic tools in medicine, we have synthesized two compounds derived from one of them in which we have joined a fluorescent dye through two linkers of different length. Our later HTS turbidity tests have shown that this two new compounds keep the inhibitor activity of their predecessor, especially that one in which the linker is longer, what is considered a satisfactory starting point for coming studies.