Molecular imaging insights into neurodegeneration: focus on α-synuclein radiotracers

Neurodegenerative diseases characterized by the presence of α-synuclein-a hallmark of pathologic inclusions termed Lewy bodies-include Parkinson's disease, dementia with Lewy bodies, and multiple-system atrophy. Although motor symptoms are related to the altered presynaptic dopaminergic function in these diseases, the appearance of α-synuclein inclusions precedes the involvement of the nigrostriatal dopaminergic pathway. Hence, the most accurate and earliest definition of premotor Parkinson's disease ought to rely on imaging α-synuclein rather than dopaminergic changes. Moreover, dopaminergic imaging has been controversial in monitoring the effects of investigational disease-modifying drugs. For these clinical trials, intense interest in longitudinally imaging α-synuclein as the primary pathologic process has led to efforts toward developing a suitable radiotracer for this key protein. An overview of the present α-synuclein radiotracer development scenario is presented here.