Metal Concentrations in Cerebrospinal Fluid and Blood Plasma from Patients with Amyotrophic Lateral Sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal degenerative disorder of motor neurons. The cause of this degeneration is unknown, and different causal hypotheses include genetic, viral, traumatic and environmental mechanisms. In this study, we have analyzed metal concentrations in cerebrospinal fluid (CSF) and blood plasma in a well-defined cohort (n = 17) of ALS patients diagnosed with quantitative electromyography. Metal analyses were performed with high-resolution inductively coupled plasma mass spectrometry. Statistically significant higher concentrations of manganese, aluminium, cadmium, cobalt, copper, zinc, lead, vanadium and uranium were found in ALS CSF compared to control CSF. We also report higher concentrations of these metals in ALS CSF than in ALS blood plasma, which indicate mechanisms of accumulation, e.g. inward directed transport. A pattern of multiple toxic metals is seen in ALS CSF. The results support the hypothesis that metals with neurotoxic effects are involved in the pathogenesis of ALS.

Risk agents related to work and amyotrophic lateral sclerosis: An occupational medicine focus

“…Metals have been studied for a long time in order to understand pathogenic mechanisms underlying development of neurodegenerative disease better, and to date there are prospects of study for this topic [71]. As for cadmium, apart from recent evidence of a high metal concentration in the cerebrospinal fluid of ALS patients [85], there are some works focusing on occupational exposures in certain employment sectors, such as production of nickel-cadmium batteries [86,87]. Some evidence in experimental models concerning neurotoxicity of other metals such as zinc and copper [88,89] is also present in scientific literature, but there is no strong evidence concerning relationship with ALS.…”

Dietary intake and zinc status in amyotrophic lateral sclerosis

“…Corroborating this, Roos et al (37) found low plasma zinc content in patients with ALS. Moreover, Peters et al (38), in a case-control study, observed an inverse association between serum zinc concentration and ALS.…”

Aluminum Toxicity and its Role in Neurodegenerative Diseases: Review

“…Dejenerasyonun sebebi bilinmemekle birlikte genetik, viral, travmatik ve çevresel mekanizmalar üzerinde durulmaktadır. 38 Metal toksisitesinin ALS ve diğer nörodejeneratif hastalıklarda risk faktörü olduğu düşünülse de 321 hastanın değerlendirildiği retrospektif bir çalışmada, idrar Al düzeylerinin normal sınırlar içinde olduğu bildirilmiştir. 39 ALS tanısı olan beş hastanın ventral servikal spinal kord örnekleri alınarak Al, Ca ve Fe düzeyleri ölçüldüğünde, Al düzeylerinin kontrole göre fark göstermediği, sadece Fe düzeylerin yük-sek olduğu saptanmıştır.…”

“…Sonuçlar ALS patogenezinde nörotoksik metallerin etkisini güçlendir-miştir. 38 Diğer taraftan ALS tanısı olan beş hasta- 43 Yapılan bu çalışmalar toksik metallerin hastalığın patofizyolojisindeki rolünü desteklemektedir.…”