Serum Amyloid Beta Peptides in Patients with Dementia and Age-Matched Non-Demented Controls as Detected by Surface-Enhanced Laser Desorption Ionisation-Time of Flight Mass Spectrometry (SELDI-TOF MS)

被引:10
作者
Frankfort, Suzanne V. [1 ,2 ]
van Campen, Jos P. C. M. [1 ]
Tulner, Linda R. [1 ]
Beijnen, Jos H. [2 ,3 ]
机构
[1] Slotervaart Hosp, Dept Geriatr Med, NL-1066 EC Amsterdam, Netherlands
[2] Slotervaart Hosp, Dept Pharm & Pharmacol, Louwesweg 6, NL-1066 EC Amsterdam, Netherlands
[3] Univ Utrecht, Fac Pharmaceut Sci, Dept Biomed Anal, Div Drug Toxicol, NL-3584 CA Utrecht, Netherlands
来源
CURRENT CLINICAL PHARMACOLOGY | 2008年 / 3卷 / 03期
关键词
D O I
10.2174/157488408785747665
中图分类号
R9 [药学];
学科分类号
1007 [药学];
摘要
Background: By using surface enhanced laser desorption/ionisation-time of flight mass spectrometry (SELDI-TOF MS) an amyloid ss (Ass) profile was shown in cerebrospinal fluid (CSF) of patients with dementia. Objective: To investigate the A beta-profile in serum with SELDI-TOF MS, to evaluate if this profile resembles CSF profiles and to investigate the correlation between intensity of A beta-peptide-peaks in serum and clinical, demographical and genetic variables. Methods: Duplicate profiling of Ass by an SELDI-TOF MS immunocapture assay was performed in 106 patients, suffering from Alzheimer's Disease or Vascular Dementia and age-matched non-demented control patients. Linear regression analyses were performed to investigate the intensities of four selected A beta peaks as dependent variables in relation to the independent clinical, demographic or genetic variables. Results: Ass37, Ass38 and Ass40 were found among additional unidentified Ass peptides, with the most pronounced Ass peak at a molecular mass of 7752. This profile partly resembled the CSF profile. The clinical diagnosis was not a predictive independent variable, however ABCB1 genotypes C1236T, G2677T/A, age and creatinine level showed to be related to Ass peak intensities in multivariate analyses. Conclusions: We found an Ass profile in serum that partly resembled the CSF profile in demented patients. Age, creatinine levels, presence of the APOE epsilon 4 allele and ABCB1 genotypes (C1236T and G2677T/A) were correlated with the A beta serum profile. The role of P-gp as an Ass transporter and the role of ABCB1 genotypes deserves further research. The investigated serum A beta profile is probably not useful in the diagnosis of dementia.
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页码:144 / 152
页数:9
相关论文
共 46 条
[1]
CSF biomarkers for mild cognitive impairment and early Alzheimer's disease [J].
Andreasen, N ;
Blennow, K .
CLINICAL NEUROLOGY AND NEUROSURGERY, 2005, 107 (03) :165-173
[2]
Evaluation of CSF-tau and CSF-Aβ42 as diagnostic markers for Alzheimer disease in clinical practice [J].
Andreasen, N ;
Minthon, L ;
Davidsson, P ;
Vanmechelen, E ;
Vanderstichele, H ;
Winblad, B ;
Blennow, K .
ARCHIVES OF NEUROLOGY, 2001, 58 (03) :373-379
[3]
Serum creatinine levels correlate with plasma amyloid β protein [J].
Arvanitakis, Z ;
Lucas, JA ;
Younkin, LH ;
Younkin, SG ;
Graff-Radford, NR .
ALZHEIMER DISEASE & ASSOCIATED DISORDERS, 2002, 16 (03) :187-190
[4]
Generation of C-terminally truncated amyloid-β peptides is dependent on γ-secretase activity [J].
Beher, D ;
Wrigley, JDJ ;
Owens, AP ;
Shearman, MS .
JOURNAL OF NEUROCHEMISTRY, 2002, 82 (03) :563-575
[5]
CSF markers for incipient Alzheimer's disease [J].
Blennow, K ;
Hampel, H .
LANCET NEUROLOGY, 2003, 2 (10) :605-613
[6]
Alzheimer's disease [J].
Blennow, Kaj ;
de Leon, Mony J. ;
Zetterberg, Henrik .
LANCET, 2006, 368 (9533) :387-403
[7]
Mammalian ABC transporters in health and disease [J].
Borst, P ;
Elferink, RO .
ANNUAL REVIEW OF BIOCHEMISTRY, 2002, 71 :537-592
[8]
Pharmacogenetic screening for polymorphisms in drug-metabolizing enzymes and drug transporters in a dutch population [J].
Bosch, T. M. ;
Doodeman, V. D. ;
SmitS, P. H. M. ;
Meijerman, I. ;
Schellens, J. H. M. ;
Beijnen, J. H. .
MOLECULAR DIAGNOSIS & THERAPY, 2006, 10 (03) :175-185
[9]
Genetic polymorphisms of drug-metabolising enzymes and drug transporters in the chemotherapeutic treatment of cancer [J].
Bosch, TM ;
Meijerman, I ;
Beijnen, JH ;
Schellens, JHM .
CLINICAL PHARMACOKINETICS, 2006, 45 (03) :253-285
[10]
P-glycoprotein deficiency at the blood-brain barrier increases amyloid-β deposition in an Alzheimer disease mouse model [J].
Cirrito, JR ;
Deane, R ;
Fagan, AM ;
Spinner, ML ;
Parsadanian, M ;
Finn, MB ;
Jiang, H ;
Prior, JL ;
Sagare, A ;
Bales, KR ;
Paul, SM ;
Zlokovic, BV ;
Piwnica-Worms, D ;
Holtzman, DM .
JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (11) :3285-3290