Early Diagnosis of Neurodegenerative Diseases: What Has Been Undertaken to Promote the Transition from PET to Fluorescence Tracers.

Alzheimer's Disease (AD) and Parkinson's Disease (PD) represent two among the most frequent neurodegenerative diseases worldwide. A common hallmark of these pathologies is the misfolding and consequent aggregation of amyloid proteins into soluble oligomers and insoluble β-sheet-rich fibrils, which ultimately lead to neurotoxicity and cell death. After a hundred years of research on the subject, this is the only reliable histopathological feature in our hands. Since AD and PD are diagnosed only once neuronal death and the first symptoms have appeared, the early detection of these diseases is currently impossible. At present, there is no effective drug available, and patients are left with symptomatic and inconclusive therapies. Several reasons could be associated with the lack of effective therapeutic treatments. One of the most important factors is the lack of selective probes capable of detecting, as early as possible, the most toxic amyloid species involved in the onset of these pathologies. In this regard, chemical probes able to detect and distinguish among different amyloid aggregates are urgently needed. In this article, we will review and put into perspective results from ex vivo and in vivo studies performed on compounds specifically interacting with such early species. Following a general overview on the three different amyloid proteins leading to insoluble β-sheet-rich amyloid deposits (amyloid β