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 ;
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
    Andreasen, N
    Blennow, K
    [J]. 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
    Andreasen, N
    Minthon, L
    Davidsson, P
    Vanmechelen, E
    Vanderstichele, H
    Winblad, B
    Blennow, K
    [J]. ARCHIVES OF NEUROLOGY, 2001, 58 (03) : 373 - 379
  • [3] Serum creatinine levels correlate with plasma amyloid β protein
    Arvanitakis, Z
    Lucas, JA
    Younkin, LH
    Younkin, SG
    Graff-Radford, NR
    [J]. ALZHEIMER DISEASE & ASSOCIATED DISORDERS, 2002, 16 (03) : 187 - 190
  • [4] Generation of C-terminally truncated amyloid-β peptides is dependent on γ-secretase activity
    Beher, D
    Wrigley, JDJ
    Owens, AP
    Shearman, MS
    [J]. JOURNAL OF NEUROCHEMISTRY, 2002, 82 (03) : 563 - 575
  • [5] CSF markers for incipient Alzheimer's disease
    Blennow, K
    Hampel, H
    [J]. LANCET NEUROLOGY, 2003, 2 (10) : 605 - 613
  • [6] Alzheimer's disease
    Blennow, Kaj
    de Leon, Mony J.
    Zetterberg, Henrik
    [J]. LANCET, 2006, 368 (9533) : 387 - 403
  • [7] Mammalian ABC transporters in health and disease
    Borst, P
    Elferink, RO
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, 2002, 71 : 537 - 592
  • [8] Pharmacogenetic screening for polymorphisms in drug-metabolizing enzymes and drug transporters in a dutch population
    Bosch, T. M.
    Doodeman, V. D.
    SmitS, P. H. M.
    Meijerman, I.
    Schellens, J. H. M.
    Beijnen, J. H.
    [J]. MOLECULAR DIAGNOSIS & THERAPY, 2006, 10 (03) : 175 - 185
  • [9] Genetic polymorphisms of drug-metabolising enzymes and drug transporters in the chemotherapeutic treatment of cancer
    Bosch, TM
    Meijerman, I
    Beijnen, JH
    Schellens, JHM
    [J]. 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
    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
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (11) : 3285 - 3290