Real-time brain imaging for diagnosing Alzheimer's disease
Age-related neurodegenerative diseases such as AD are on a steady rise, negatively affecting the quality of life of patients and their families. Disease aetiology has been attributed to misfolded protein molecules, called amyloids, which accumulate in the brain and corrupt normal cellular functions. The blood-brain barrier (BBB) hampers the efficacy of therapies as it limits access to the brain and central nervous system. Scientists of the EU-funded 'Luminescent polymers for in vivo imaging of amyloid signatures' (LUPAS) project worked to develop novel agents and imaging methods. They utilised reporter molecules based on luminescent conjugated polymers called luminescent conjugated polythiophenes (LCPs). The project website contains extensive information on LUPAS objectives and deliverables. LCPs are highly selective and specific when it comes to targeting protein aggregates with their luminescence making them ideal for imaging purposes. LCPs were also considered for their therapeutic potency as they can cross the blood–brain barrier (BBB) and behave like structural chameleons. In other words, they can alter their shape and colour upon binding to amyloid targets of different structure. The LUPAS consortium selected 20 novel anionic LCPs for the selective identification of protein deposits from a library of chemically defined oligothiophenes. For non-invasive imaging, the consortium had to turn to magnetic resonance imaging (MRI). To increase the MR signal, scientists made use of targeted contrast agents based on paramagnetic and super-paramagnetic nanoparticles and nanocomplexes. Conjugation of these agents to LCPs was achieved by LUPAS and these novel multimodal agents showed promising amyloid targeting in vitro and in vivo. Work on tissue sections and cell cultures demonstrated that LCPs stabilised prion aggregates and reduced their infectivity. This insight opened up new avenues for therapeutic targeting of prion diseases. The LUPAS-developed LCPs offer a smart way of targeting misfolded protein or amyloid lesions encountered in neurodegenerative disorders. Their implementation in clinical practice would address the tremendous need for quantitative techniques that can enable diagnosis and treatment of these diseases.
