Is serotonin pathology a good biomarker in vivo for early Parkinson’s disease?

Parkinson’s disease (PD) is a neurodegenerative disorder characterized pathologically by the aggregation of alpha-synuclein (SNCA), which is the main component of Lewy bodies, and the loss of dopaminergic neurons in the substantia nigra (1). Although progressive dopaminergic denervation is the cardinal pathology in PD, in the last decades several studies have shown that other systems are affected as well. The serotonergic system, originating from the brainstem raphe nuclei, is known to be disrupted in PD. Multiple preclinical and in vivo works provide evidence for this. Neuropathologic studies have shown a loss of serotonergic cell bodies with Lewy aggregates in the raphe nuclei (2) along with reduced serotonergic markers in striatum (3,4), hypothalamus and frontal cortex (4), although not to the same degree as dopamine loss. Molecular imaging studies using the second generation PET ligand [11C]-3-Amino-4-(2-dimethylaminomethylphenylsulfaryl)-benzonitrile (DASB) have demonstrated in vivo changes of presynaptic 5-HT transporter (SERT) and postsynaptic serotonergic receptors targets in sporadic (5) and genetic PD patients (6). Other studies, mainly using neuroimaging techniques, have linked serotonin deficiency with some common non-motor symptoms such as depression, sleep disorder and fatigue (7-9) in Parkinson patients at different stages of disease. Additionally, several works have associated levodopa induced dyskinesia to non-physiological release of dopamine leaded by an imbalanced dopaminergic to serotonergic terminal ratio, with the later playing a main key role (10)