Abstract
Background: Amyotrophic lateral sclerosis (ALS) is a rare motor neurodegenerative disorder and is predominantly diagnosed in older adults. Altered levels of essential and toxic elements have been associated with ALS risk, but little is known about the time-varying biodynamic synchronization of elements and their association with ALS risk.
Method: Using a single individual hair strand, we generated time series data of 400-800 time points approximately at 2 to 4 hourly resolution on 17 elemental intensities in ALS cases and controls from a national collection and a regional center in the US (on a total sample of 391, with 295 cases and 96 controls, and median age over 60 years). The elements included were Li, Mg, P, S, Ca, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Sr, Sn, Ba, and Pb. We analyzed the growth increments in single hair strands using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to create time-resolved signals of elemental exposure and intensity along the hair strand. Two complementary information-theoretic methods, cross-recurrence quantification and transfer entropy-based network analysis, were used to generate time-resolved features that quantify synchronization of the elemental biodynamics.
Findings: Male ALS cases had significantly lower synchronicity in Cu-Zn recurrence than controls (log(β) = -1.64, p=0.00004, qvalue = 0.03). Female ALS cases had lower synchronicity in Cr-Ni recurrence than controls (log(β) = -1.59, p=0.0007, qvalue = 0.46). In both males and females, multiple centrality measures of Cu (that quantify the importance of Cu within a network of all elements) were significantly lower in cases than in controls [in males, closeness centrality of Cu: log(β) = -0.64, p=0.002, qvalue = 0.04; in females, eigenvector centrality of Cu: log(β) = -0.53, p=0.02, qvalue = 0.97].
Interpretation: We show that ALS cases have significantly higher odds of collapse in synchronization in the elemental biodynamics and worse connectedness in copper-based networks than in controls.
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