Human tissue lead (Pb) levels and amyotrophic lateral sclerosis: a systematic review and meta-analysis of case–control studies

Abstract

Aim To combine the current scientific literature evidence and elucidate the differences of lead (Pb) bioaccumulation in human tissues by comparing amyotrophic lateral sclerosis (ALS) patients and healthy controls. Methods We systematically searched for case–control studies on the association of Pb levels with ALS, in human cells, tissues, and body fluids (nervous tissue, muscle, blood, cerebrospinal fluid, urine, skin appendages). Then, we performed a meta-analysis for all the tissues in which at least five case–control studies were available: whole blood (9 studies), serum/plasma (5 studies), and cerebrospinal fluid (CSF) (6 studies). Differences between cases and controls were evaluated using standardized mean difference, and combined estimates were derived using random effect maximum likelihood (REML) meta-analyses. Results Among 1734 records, we identified 46 full-text studies, of which 14 case–control studies met the meta-analysis inclusion criteria. We found higher Pb levels in ALS cases than controls in blood (standardized mean difference (SMD) = 0.61; 95% confidence interval (CI) 0.20, 1.01; p = 0.003), plasma/serum (SMD = 0.27; 95% CI − 0.16, 0.70; p = 0.26), and CSF (SMD = 0.53; 95% CI − 0.09, 1.15; p = 0.09). Conclusions This work provides further evidence of the association between Pb bioaccumulation and ALS in body fluids. The lack of association studies in solid tissues did not allow a robust meta-analysis. Future prospective studies are needed to clarify the causality in the association of Pb bioaccumulation with ALS.

Quantitative association between lead exposure and amyotrophic lateral sclerosis: a Bayesian network-based predictive study

“…Case-control studies found higher Pb levels in ALS cases than controls in blood from a statistical view. However, statistically significant results were not observed for tissues like plasma/serum and cerebrospinal fluid (CSF) ( [ 5 ]). It has been proved that Pb tended to accumulate inside the erythrocytes rather than into the plasma component ( [ 17 ]).…”

“…Pb associated with several neurodegenerative diseases, like ALS, Alzheimer’s disease (AD), Parkinson’s disease (PD) ( [ 4 ]). A meta-analysis of 14 case-control studies found statistically higher Pb levels in ALS cases than controls in whole blood samples ( [ 5 ]). Our unpublished data provided novel evidence that Pb caused abnormal aggregation of SOD-1 in motor neurons by interfering with the chaperone functions of Glucose-Regulated Protein of 78 kDa (GRP78).…”

Impairments of Spatial Memory and N-methyl-d-aspartate Receptors and Their Postsynaptic Signaling Molecules in the Hippocampus of Developing Rats Induced by As, Pb, and Mn Mixture Exposure

“…Metals are introduced into the environment as mixtures from various anthropogenic sources such as mining, refining, the smelting of ores, or agriculture and natural activities [1,2]. The exposure of human beings to arsenic (As), lead (Pb), and manganese (Mn) through water and foods has raised increasing concerns about health risks [3][4][5]. The interactions of metals in these mixtures can influence their uptake and deposition in organs, which may eventually amplify the overall toxicity in exposed organisms [6][7][8].…”