Abstract
In this study, the quotients (Q) between metal concentrations in cerebrospinal fluid (CSF) and plasma were studied in subjects with Alzheimer’s disease (AD) and referents to investigate if the leakage through the blood–CSF barrier (BCB) increased with increased duration and severity of the disease. Concentrations of 18 metals (Mg, Ca, Mn, Fe, Co, Ni, Cu, Zn, Se, Rb, Sr, Mo, Cd, Sn, Sb, Cs, Hg, and Pb) were determined by ICP-MS in plasma and cerebrospinal fluid in 264 patients with AD, and in 54 healthy referents. The quotients Q Mn, Q Rb, Q Sb, Q Pb and Q Hg were significantly lower (p ≤ 0.003) and Q Co significantly higher (p ≤ 0.001) in subjects with AD as compared with the controls. Subjects in a subgroup with more severe AD, showed the same pattern. The metal leakage into CSF did not increase with increased duration and/or severity of the disease. The permeability of BCB varied considerably between the studied metals with low median quotients (Q ≤ 0.02) for Cd, Cu, Sb, Se and Zn and higher median quotients for Ca (Q ~ 0.5) and Mg (Q ~ 1.3), probably partly depending on differences in size and lipophilicity of metal–carrier complexes and specific carrier mechanisms.
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References
Altman DG (1991) Practical statistics for medical research. Chapman & Hall, London
American Psychiatric Association (1994) Diagnostic and statistical manual of psychiatric disorders, 4th edn (DSM IV). American Psychiatric Association, Washington
Aschner M, Clarkson TW (1988) Distribution of mercury 203 in pregnant rats and their fetuses following systemic infusions with thiol-containing amino acids and glutathione during late gestation. Teratology 38:145–155
Bárány E, Bergdahl IA, Schütz A, Skerfving S, Oskarsson A (1997) Inductively coupled plasma mass spectrometry for direct multi-element analysis of diluted human blood and serum. J Anal Atomic Spectrom 12:1005–1009
Bressler JP, Olivi L, Cheong JH, Kim Y, Maerten A, Bannon D (2007) Metal transporters in intestine and brain: their involvement in metal-associated neurotoxicities. Hum Exp Toxicol 26:221–229
Choudhuri S, Cherrington NJ, Li N, Klaassen CD (2003) Constitutive expression of various xenobiotic and endobiotic transporter mRNAs in the choroid plexus of rats. Drug Metab Dispos 31:1337–1345
Folstein MF, Folstein SE, McHugh PR (1975) “Mini mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198
Forte G, Bocca B, Senofonte O, Petrucci F, Brusa L, Stanzione P et al (2004) Trace and major elements in whole blood, serum, cerebrospinal fluid and urine of patients with Parkinson’s disease. J Neural Transm 111:1031–1040
Gerhardsson L, Lundh T, Minthon L, Londos E (2008) Metal concentrations in plasma and cerebrospinal fluid in patients with Alzheimer’s disease. Dement Geriatr Cogn Disord 25:508–515
Gerhardsson L, Blennow K, Lundh T, Londos E, Minthon L (2009) Concentrations of metals, β-amyloid and tau-markers in cerebrospinal fluid in patients with Alzheimer’s disease. Dement Geriatr Cogn Disord 28:88–94
McKhann G, Drachmann D, Folstein M, Kattzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS–ADRDA Work group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology 34:939–944
Mohs RC, Rosen WG, Davis KL (1983) The Alzheimer’s disease assessment scale: an instrument for assessing treatment efficacy. Psychopharmacol Bull 19:448–450
Nischwitz V, Berthele A, Michalke B (2008) Speciation analysis of selected metals and determination of their total contents in paired serum and cerebrospinal fluid samples: an approach to investigate the permeability of the human blood–cerebrospinal fluid-barrier. Anal Chim Acta 627:258–269
Roman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH et al (1993) Vascular dementia: diagnostic criteria for research studies. Report of the NINDS–AIREN International Workshop. Neurology 43:250–260
Sandborg-Englund G, Elinder CG, Langworth S, Schütz A, Ekstrand J (1998) Mercury in biological fluids after amalgam removal. J Dent Res 77:615–624
Stomrud E, Hansson O, Blennow K, Minthon L, Londos E (2007) Cerebrospinal fluid biomarkers predict decline in subjective cognitive function over 3 years in healthy elderly. Dement Geriatr Cogn Disord 24:118–124
Szmydynger-Chodobska J, Chodobski A, Johanson CE (1994) Postnatal developmental changes in blood flow to choroid plexuses and cerebral cortex of the rat. Am J Physiol 266(5 Pt 2):R1488–R1492
Tian JZ, Shi J, Zhang XQ, Bi Q, Ma X, Wang ZL et al (2008) Guiding principles of clinical research on mild cognitive impairment (protocol). Zhong Xi Yi Jie He Xue Bao 6:9–14 In Chinese
Yokel RA (2006) Blood–brain barrier flux of aluminum, manganese, iron and other metals suspected to contribute to metal-induced neurodegeneration. J Alzheimer’s Disease 10:223–253
Zheng W (2001) Toxicology of choroid plexus: special reference to metal-induced neurotoxicities. Microsc Res Tech 52:89–103
Zheng W, Perry DF, Nelson DL, Aposhian HV (1991) Choroid plexus protects cerebrospinal fluid against toxic metals. FASEB J 5:2188–2193
Zheng W, Aschner M, Ghersi-Egea JF (2003) Brain barrier systems: a new frontier in metal neurotoxicological research. Toxicol Appl Pharmacol 192:1–11
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Gerhardsson, L., Lundh, T., Londos, E. et al. Cerebrospinal fluid/plasma quotients of essential and non-essential metals in patients with Alzheimer’s disease. J Neural Transm 118, 957–962 (2011). https://doi.org/10.1007/s00702-011-0605-x
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DOI: https://doi.org/10.1007/s00702-011-0605-x