A major goal of current clinical research in Parkinson’s disease (PD) is the validation and standardization of biomarkers enabling early diagnosis, predicting outcomes, understanding PD pathophysiology, and demonstrating target engagement in clinical trials. Molecular imaging with specific dopamine-related tracers offers a practical indirect imaging biomarker of PD, serving as a powerful tool to assess the status of presynaptic nigrostriatal terminals. In this review we provide an update on the dopamine transporter (DAT) imaging in PD and translate recent findings to potentially valuable clinical practice applications. The role of DAT imaging as diagnostic, preclinical and predictive biomarker is discussed, especially in view of recent evidence questioning the incontrovertible correlation between striatal DAT binding and nigral cell or axon counts.

The diagnosis of neurodegenerative diseases (NDDs) represents an increasing social burden, with the unsolved issue of disease-modifying therapies (DMTs). The failure of clinical trials treating Alzheimer′s Disease (AD) so far highlighted the need for a different approach in drug design and patient selection. Identifying subjects in the prodromal or early symptomatic phase is critical to slow down neurodegeneration, but the implementation of screening programs with this aim will have an ethical and social aftermath. Novel minimally invasive candidate biomarkers (derived from blood, saliva, olfactory brush) or classical cerebrospinal fluid (CSF) biomarkers have been developed in research settings to stratify patients with NDDs. Misfolded protein accumulation, neuroinflammation, and synaptic loss are the pathophysiological hallmarks detected by these biomarkers to refine diagnosis, prognosis, and target engagement of drugs in clinical trials. We reviewed fluid biomarkers of NDDs, considering their potential role as screening, diagnostic, or prognostic tool, and their present-day use in clinical trials (phase II and III). A special focus will be dedicated to novel techniques for the detection of misfolded proteins. Eventually, an applicative diagnostic algorithm will be proposed to translate the research data in clinical practice and select prodromal or early patients to be enrolled in the appropriate DMTs trials for NDDs.

Background: Monoclonal antibodies against the calcitonin gene-related peptide (anti-CGRP mAbs) have been a game-changer in migraine treatment over the last decade. However, data regarding the reduction in the frequency of episodes of migraine with aura are limited, as no trials have been specifically designed to evaluate this outcome. Methods: In this narrative review, we summarized clinical data from both randomized controlled trials (RCTs) and real-world studies (RWSs) on the efficacy and effectiveness of anti-CGRP mAbs in patients with migraine with aura and aura symptoms. Results: Overall, anti-CGRP mAbs can reduce migraine frequency and burden regardless of the presence of aura, with efficacy and effectiveness in both patients with and without aura. A few studies suggested a potential influence on reducing aura occurrence. However, several limitations affect the available studies and prevent definitive conclusions regarding the effects of anti-CGRP mAbs on aura. Conclusions: Further studies specifically aimed at assessing the impact of anti-CGRP therapies on the frequency, duration, and characteristics of aura are necessary. Such research could help elucidate the complex relationship between CGRP and aura.