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)
Suzanne V. Frankfort, Jos P.C.M. van Campen, Linda R. Tulner and Jos H. Beijnen
Affiliation: Department of Pharmacy&Pharmacology, Slotervaart Hospital, Louwesweg 6, 1066 EC Amsterdam, The Netherlands.
Keywords: Serum Amyloid Beta Peptides, dementia, SELDI-TOF MS, Alzheimer's Disease, CSF profile, diagnosis, DNA Isolation, Genotype Analysis
Background: By using surface enhanced laser desorption/ionisation- time of flight mass spectrometry (SELDITOF MS) an amyloid ß (Aß) profile was shown in cerebrospinal fluid (CSF) of patients with dementia. Objective: To investigate the Aβ-profile in serum with SELDI-TOF MS, to evaluate if this profile resembles CSF profiles and to investigate the correlation between intensity of Aβ-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 Alzheimers Disease or Vascular Dementia and age-matched non-demented control patients. Linear regression analyses were performed to investigate the intensities of four selected Aβ 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 ε4 allele and ABCB1 genotypes (C1236T and G2677T/A) were correlated with the Aβ serum profile. The role of P-gp as an Aß transporter and the role of ABCB1 genotypes deserves further research. The investigated serum Aβ profile is probably not useful in the diagnosis of dementia.
Rights & PermissionsPrintExport