title: Patterns of levels of biological metals in CSF differ among neurodegenerative diseases.
abstract: We measured the levels of some biological metals: copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), and zinc (Zn) in the cerebrospinal fluid (CSF) in patients with neurodegenerative diseases (52 patients with amyotrophic lateral sclerosis (ALS)), 21 patients with Alzheimer's disease (AD), and 20 patients with Parkinson's disease (PD) by inductively coupled plasma mass spectrometry (ICP-MS). The diagnoses were additionally supported by neuroimaging techniques for AD and PD. In ALS, the levels of Mg (p<0.01 significant difference), Fe, Cu (p<0.05), and Zn (p<0.10) in CSF were higher than those in controls. Some patients showed very high levels of Cu and Zn before the critical deterioration of the disease. In AD, the levels of Cu and Zn in CSF were significantly higher in patients with late-onset AD (p<0.01). In PD, we found significantly increased levels of especially Cu and Zn in particular (p<0.01) and Mn (p<0.05) in CSF. A multiple comparison test suggested that the increased level of Mg in ALS and that of Mn in PD were the pathognomonic features. These findings suggest that Cu and Zn in particular play important roles in the onset and/or progression of ALS, AD, and PD. Therefore, Cu-chelating agents and modulators of Cu and Zn such as metallothionein (MT) can be new candidates for the treatment of ALS, AD, and PD.
authors.affiliation: Department of Neurology and Geriatrics, Gifu University, Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. ihozumi@gifu-u.ac.jp
authors.forename: Isao
authors.initials: I
authors.lastname: Hozumi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Akiko
authors.initials: A
authors.lastname: Honda
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ozawa
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Kazunori
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Megumi
authors.initials: M
authors.lastname: Yamada
authors.forename: Akihiro
authors.initials: A
authors.lastname: Koumura
authors.forename: Takeo
authors.initials: T
authors.lastname: Sakurai
authors.forename: Akio
authors.initials: A
authors.lastname: Kimura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Masahiko
authors.initials: M
authors.lastname: Satoh
authors.forename: Takashi
authors.initials: T
authors.lastname: Inuzuka
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000473:pathology; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid / Q000473:pathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D013058:Mass Spectrometry; D008670:Metals / Q000134:cerebrospinal fluid*; D019216:Metals, Heavy / Q000134:cerebrospinal fluid; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000134:cerebrospinal fluid* / Q000473:pathology; D010300:Parkinson Disease / Q000134:cerebrospinal fluid / Q000473:pathology
chemical_list: D008670:Metals; D019216:Metals, Heavy