Molecular imaging in neurodegenerative diseases

Neurodegenerative diseases are characterized by progressive neuronal loss due to the accumulation of misfolded proteins into the brain, underpinned by complex gene – environment interactions. Clinical diagnosis of such conditions, such as Alzheimer’s and Parkinson’s diseases (AD, PD), primarily relies on clinical assessment, with post-mortem evaluation being considered the gold standard for definite pathological diagnosis. Recent advances in structural and functional imaging, however, have led to the availability of techniques allowing the evaluation and quantification of pathophysiological processes underlying neurodegeneration in vivo. It is the case of molecular neuroimaging techniques, including positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging which, with ad hoc radioligands, allow the in vivo evaluation of multiple pathogenic pathways. These include different ligands evaluating the specific abnormal protein aggregation leading to neurodegeneration (e.g. amyloid and tau), used for diagnostic purposes or as target of disease-modifying treatment. In addition to this, molecular imaging enables the evaluation of new ligands altered brain glucose metabolism (using 18F-FDG PET), altered density of neurotransmitters receptors and transporters (e.g. dopamine and serotonin), as well as brain inflammation (e.g. microglia activation, using 11C-PK11195). A growing body of evidence suggests that these techniques can provide invaluable diagnostic and prognostic potential in neurodegeneration, even in early disease stages, in some cases allowing robust definition of the underlying disease. Other PET ligands investigating alternative targets, such as 11C-UCB-J indexing synaptic density, are currently under evaluation and hold great promise for a further understanding of neurodegenerative conditions. 
The aim of this research topic of Frontiers in Neuroscience is to welcome groundbreaking original articles investigating PET/SPECT imaging potential in both clinical and research applications. This is particularly timely given the increasing diffusion of these techniques worldwide, and their progressive inclusion in clinical trials as both screening tools and outcome evaluation measures. With the approval of some of these novel techniques for clinical use (e.g. amyloid-PET in Europe and US, as well as tau-PET in the US), and the new era of disease-modifying treatment tested in several neurodegenerative disorders this special issue will also welcome submissions investigating the value of such techniques in clinical, non-research settings, highlighting their strengths and weaknesses also in more diverse populations. 
In addition to clinical and other biological markers, molecular imaging (including novel MRI-based molecular imaging) will certainly contribute to gain further insight into the complex pathophysiological mechanisms involved in neurodegeneration and to help developing and/or evaluating disease-modifying treatments.