Serotonergic pathology and Braak's staging hypothesis in Parkinson's disease

• Published in: Lancet neurology Vol. 18; no. 8; pp. 713 - 714
• Main Authors: Schindlbeck, Katharina A, Eidelberg, David
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-08-2019; Elsevier Limited
• Subjects: Brain stem; Dopamine; Dopamine transporter; Emotional behavior; Hypotheses; Levodopa; Lewy bodies; Longitudinal studies; Movement disorders; Mutation; Nervous system; Neurodegenerative diseases; Parkinson's disease; Pathology; Phenotypes; Positron emission tomography; Serotonin; Serotonin transporter; Synuclein; Tremor; Wilson, Heather
• ISSN: 1474-4422; 1474-4465
• DOI: 10.1016/S1474-4422(19)30242-X

The gene encoding for α-synuclein (SNCA) was the first to be linked to familial Parkinson's disease.1 At the same time, α-synuclein was identified as the main component of Lewy bodies, which are present in both familial and idiopathic Parkinson's disease.2 The Ala53Thr (A53T) SNCA mutation is associated with a similar clinical phenotype to the sporadic disease, albeit with earlier age-of-onset and faster disease progression.3,4 In The Lancet Neurology, Heather Wilson and colleagues5 report findings from a PET imaging study in A53T SNCA mutation carriers with (n=7) and without (n=7) clinically manifest Parkinson's disease, compared with patients with idiopathic Parkinson's disease (n=25)and healthy controls (n=25). The severity of the serotonin transporter loss in premotor carriers was noted to be at levels typically seen in idiopathic patients. [...]carriers with manifest disease showed greater loss of both serotonin and dopamine transporters in the caudate compared with age-matched idiopathic patients. Localised decreases in serotonergic transporter binding are a common finding in patients with Parkinson's disease, and have been associated with a variety of symptoms, including tremor and levodopa-mediated dyskinesias, and non-motor symptoms such as depression, fatigue, apathy, and weight changes.7 In the present study, brainstem serotonergic binding loss correlated with motor and non-motor symptoms in idiopathic Parkinson's disease patients and in A53T SNCA carriers with and without manifest disease.