Publikationsrepositorium - Helmholtz-Zentrum Dresden-Rossendorf

Einleitung
In Alzheimer’s disease (AD), there is growing evidence for the brain nicotinic acetylcholine receptors (nAChRs) being reduced at very early disease stages (in transgenic Tg2576 mice even earlier than beta-amyloid plaque deposition [Int J Devl Neurosci 2003]) and for this reduction being strongly associated with cognitive decline. Our group aims at developing and testing new nAChR positron emission tomography (PET) tracers with the goal to improve early dementia diagnosis.
Methode
We tested A85380, an ¹⁸F-labeled PET tracer which binds to the α4β2-subunit of the nAChR, and could show that nAChRs are highly significantly reduced in brain areas affected by AD-pathology in patients with early AD (correlating significantly with impaired cognition), and even in subjects with MCI who later progressed to AD [Eur J Nucl Med Mol Imaging 2011]. Using A85380, however, PET imaging of up to seven hours is required. This limitation encouraged to search for better suited tracers to be used as biomarkers in clinical routine. As a result we developed the 18F-labeled epibatidine derivative NCFHEB [Synapse 2008]. The first-in-man study testing this tracer in AD-patients and healthy controls (HCs) is ongoing. First results show that this tracer might allow imaging of nAChRs in a 20 minutes scan within 90 minutes and a significantly lower tracer binding in AD-patients compared to HCs.
Diskussion/Ergebnisse
Taken together, we were successful in the implementation of PET to image nAChRs in dementia. Our PET results support the concept of the nicotinic system being involved at early AD stages, providing motivation to further develop PET imaging for early AD diagnosis, prognosis, and therapy control.