title: Cerebrospinal fluid of newly diagnosed amyotrophic lateral sclerosis patients exhibits abnormal levels of selenium species including elevated selenite.
abstract: Exposure to selenium, and particularly to its inorganic forms, has been hypothesized as a risk factor for amyotrophic lateral sclerosis (ALS), a fast progressing motor neuron disease with poorly understood etiology. However, no information is known about levels of inorganic and some organic selenium species in the central nervous system of ALS patients, and recent observations suggest that peripheral biomarkers of exposure are unable to predict these levels for several Se species including the inorganic forms. Using a hospital-referred case-control series and advanced selenium speciation methods, we compared the chemical species of selenium in cerebrospinal fluid from 38 ALS patients to those of 38 reference neurological patients matched on age and gender. We found that higher concentrations of inorganic selenium in the form of selenite and of human serum albumin-bound selenium were associated with increased ALS risk (relative risks 3.9 (95% confidence interval 1.2-11.0) and 1.7 (1.0-2.9) for 0.1μg/L increase). Conversely, lower concentrations of selenoprotein P-bound selenium were associated with increased risk (relative risk 0.2 for 1μg/L increase, 95% confidence interval 0.04-0.8). The associations were stronger among cases age 50 years or older, who are postulated to have lower rates of genetic disease origin. These results suggest that excess selenite and human serum albumin bound-selenium and low levels of selenoprotein P-bound selenium in the central nervous system, which may be related, may play a role in ALS etiology.
authors.affiliation: CREAGEN - Environmental, Genetic and Nutritional Epidemiology Research Center, Department of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: marco.vinceti@unimore.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Vinceti
authors.forename: Nikolay
authors.initials: N
authors.lastname: Solovyev
authors.forename: Jessica
authors.initials: J
authors.lastname: Mandrioli
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Crespi
authors.forename: Francesca
authors.initials: F
authors.lastname: Bonvicini
authors.forename: Elisa
authors.initials: E
authors.lastname: Arcolin
authors.forename: Eleni
authors.initials: E
authors.lastname: Georgoulopoulou
authors.forename: Bernhard
authors.initials: B
authors.lastname: Michalke
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D020887:Selenious Acid / Q000134:cerebrospinal fluid*; D018036:Selenium Compounds / Q000134:cerebrospinal fluid*; D051149:Selenoprotein P / Q000134:cerebrospinal fluid*
chemical_list: D018036:Selenium Compounds; D051149:Selenoprotein P; D020887:Selenious Acid
keywords: Amyotrophic lateral sclerosis; Case–control study; Cerebrospinal fluid; Environment; Risk; Selenite; Selenium; Selenoprotein-P; Speciation analysis