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Key Points Question Does the pathological α-synuclein (αSyn P ) detected by immunohistochemistry in the skin of individuals with Parkinson disease (PD) have aggregation seeding activity, and is skin αSyn P seeding activity a potential biomarker for diagnosis of PD and other synucleinopathies? Findings In this diagnostic study including skin samples from 160 autopsies and 41 biopsies, a statistically significant increase in αSyn P seeding activity was observed in individuals with PD and synucleinopathies compared with controls with tauopathies and nonneurodegenerative diseases. Meaning Skin αSyn P has aggregation seeding activity in patients with PD and non-PD synucleinopathies and may be a biomarker for antemortem diagnosis of PD and other synucleinopathies.

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We studied the effect of an acute infusion of quinolinic acid (QUIN) on in vivo hydroxyl radical (.OH) formation in the striatum of awake rats. Using the microdialysis technique, the generation of.OH was assessed through electrochemical detection of the salicylate hydroxylation product 2,3-dihydroxybenzoic acid (2,3-DHBA). The .OH extracellular levels increased up to 30 times over basal levels after QUIN infusion (240 nmol/microl), returning to the baseline 2 h later. This response was attenuated, but not abolished, by pretreatment with the NMDA receptor antagonist MK-801 (10 mg/kg, i.p.) 60 min before QUIN infusion. The mitochondrial toxin 3-nitropropionic acid (3-NPA, 500 nmol/microl) had stronger effects than QUIN on .OH generation, as well as on other markers of oxidative stress explored as potential consequences of .OH increased levels. These results support the hypothesis that early .OH generation contributes to the pattern of toxicity elicited by QUIN. The partial protection by MK-801 suggests that QUIN neurotoxicity is not completely explained through NMDA receptor overactivation, but it may also involve intrinsic QUIN oxidative properties.

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