Objective: To assess alpha-synuclein pathology and tyrosine hydroxylase (TH) immunoreactivity as a dopaminergic marker in three hypothalamic nuclei with potential clinical implications (paraventricular, supraoptic and infundibular nuclei) at different stages of the disease and with different severity of NMS.

Background: Hypothalamic dysfunction may be responsible of some of the NMS in Parkinson’s disease (PD). Histological changes in PD involve the hypothalamus but their correlation with NMS symptomatology and disease progression is unknown.

Methods: Eight patients with PD and moderate-severe NMS (PD+NMS), 7 with PD with absent-mild NMS (PD-NMS), 7 with incidental Lewy body disease and 6 healthy controls were selected from the Queen Square Brain Bank archives. All groups were matched by age and patients with PD were also matched by disease duration and Braak stage. The presence of NMS was graded as absent, mild, moderate or severe based on clinical impression using clinical records. Formalin-fixed hypothalamic tissue was sampled and stained using immunohistochemistry for alpha-synuclein and TH. Alpha-synuclein and TH immunoreactivity were assessed using semiquantitative grading in the hypothalamic paraventricular, infundibular and supraoptic nuclei.

Results: Alpha-synuclein pathology could be found in all the hypothalamic nuclei in patients with PD and also in some patients with incidental Lewy body disease (14.3% paraventricular, 40% infundibular and 16.7% supraoptic). Alpha-synuclein deposition was more severe in PD+NMS group in comparison to incidental Lewy body disease (paraventricular p=0.001, infundibular p=0.02 and supraoptic p=0.008) but there were no differences when compared to PD-NMS in the three hypothalamic nuclei (paraventricular p=0.2, infundibular p=0.92 and supraoptic p=1). There were no differences in the intensity of TH immunoreactivity in the hypothalamic nuclei between any groups.

Conclusions: Alpha-synuclein involvement of the hypothalamus in PD is common, progressive, can occur at early (pre-motor) stages of the disease but it is not clinically correlated with the severity of NMS. TH immunoreactivity was similar in all the nuclei for all the groups suggesting that dopaminergic hypothalamic systems are preserved in PD.

This study will be presented at the 117th Meeting of the Bristish Neuropathological Society, 2-4th March 2016.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/hypothalamic-alpha-synuclein-pathology-and-its-relation-to-non-motor-symptoms-and-disease-progression-in-parkinsons-disease/