Alzheimer’s disease (AD) is a neurodegenerative disease and the primary diagnosed cause for dementia. Symptoms include loss of cognitive abilities and confusion, increased forgetfulness, decreased language skills, and behavioral changes. The disease often results in hippocampal atrophy; the progressive degeneration of the hippocampus. Build up of amyloid beta (Aꞵ) plaque and neufibrillic tangle of tau-protein has been discovered to block the neuron's transport system and thereby the synaptic communication, causing atrophy. There are currently no known cures for AD. Though symptoms can be slowed by treatment, degradation has already begun when symptoms are detected and cannot be stopped. However, if there was a method for detecting abnormal levels of plaques and protein build up before the patient shows any symptoms, the medical field would be put in a much better position to hinder the development of the disease.

Luminescent Conjugated Oligothiophenes (LCO) are fluorescent biomarkers that have been developed to identify targeted protein inclusion bodies. Many of the LCOs target AD-related proteins, such as the Aꞵ- or tau protein, and fluoresces when bound. This, along with the fact that the ligands are believed to be non-toxic and capable of passing the blood-brain barrier, makes the ligands potentially suitable for in vivo diagnostics of AD through detection of emitted fluorescence.

To further investigate the possibility of using LCO-ligands to detect early-stage AD, the two ligands q-FTAA-CN and b-TVBT4 were examined through molecular dynamic simulations. The aim was to investigate how the q-FTAA-CN-ligand interacts with the Aꞵ-protein by finding potential binding sites and binding strengths. The b-TVBT4 ligand selectively binds to tau-protein and was instead investigated for its fluorescent properties using quantum mechanical simulations, with the aim of determining why the molecule fluoresces when bound to tau-protein but not otherwise.

The results show that the q-FTAA-CN ligand primarily binds to the Aꞵ-protein at two different sites, where one of the sites seems to have stronger binding interactions. The interactions are primarily dominated by Coulombic forces, where the amino acid residues lysine, phenylalanine and valine interact with the probe at the stronger binding site. Lysine is also present at the weaker binding site. The ligand b-TVBT4 rapidly changes conformation in the excited state. The conformation change leads to the orbitals populated in the ground state no longer overlapping with those in the excited state. As a consequence, the transition from the excited to the ground state is no longer coupled to light and no fluorescence occurs. Hence, the fluorescence of b-TVBT4 is deactivated by internal conversion. When bound to tau-protein b-TVBT4 is prevented from changing its conformation and this can be concluded as the reason why fluorescence is not deactivated.