Objective: To test the hypothesis that certain metals may cause cellular damage suggesting tauopathy. This is an early step in testing the hypothesis that environmental metals contribute to the etiology of progressive supranuclear palsy (PSP).

Background: Case-control surveys of PSP implicate lesser education and well water use as risk factors, but the only proven PSP cluster centers on Wattrelos, in northern France, with 100 unrelated affecteds and an observed/expected incidence of 12.3. Metals processing and dumping of ore waste, especially chromate, in residential areas occurred there over much of the 20th Century.

Method: We used neuronal cell models to investigate the neurotoxic effects of three heavy metals (chromium, nickel and cadmium), which we found to be especially enriched in home-grown thyme in the area of the French cluster. We evaluated thyme because it is intensively used in French cooking and because it is known to avidly take up multiple metals from soil.

Results: We found that induced pluripotent stem cells (iPSC)-derived iNeurons from a MAPT mutation carrier were more sensitive to Cr and Ni exposure compared to an isogenic control line, suggesting that genetic variations may predispose to neurodegeneration induced by Cr and Ni. Furthermore, using a neuroblastoma cell line, we showed that both Cr and Ni induced cell death by an apoptotic mechanism. Interestingly, Cr and Ni treatments increased total tau levels in both iNeurons and SH-SY5Y cells, correlating Cr and Ni exposure with tau pathology.

Conclusion: Chronic exposure to some heavy metals could contribute to the pathophysiology and etiology of PSP.

References: Caparros-Lefebvre D, Golbe LI, Deramecourt V, et al (2015) A geographical cluster of progressive supranuclear palsy in northern France. Neurology 85(15):1293-300. Golbe LI, Rubin RS, Cody RP, et al (1996) Follow-up study of risk factors in progressive supranuclear palsy. Neurology 47:148–54. Litvan I, Lees PSJ, Cunningham CR, et al (2016) Environmental and occupational risk factors for progressive supranuclear palsy: Case-control study. Mov Disord 31:644–52. Vidal JS, Vidailhet M, Derkinderen P, et al (2009) Risk factors for progressive supranuclear palsy: a case-control study in France. J Neurol Neurosurg Psychiatry 80:1271–1274.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/heavy-metals-implicated-in-a-geographical-cluster-of-progressive-supranuclear-palsy-induce-tau-accumulation-and-apoptotic-cell-death-in-cultured-neurons/