Total ApoE and ApoE4 Isoform Assays in an Alzheimer's Disease Case-control Study by Targeted Mass Spectrometry (n = 669): A Pilot Assay for Methionine-containing Proteotypic Peptides
Abstract:Allelic polymorphism of the apolipoprotein E (ApoE) gene (ApoE 2, ApoE 3 and ApoE 4 alleles) gives rise to three protein isoforms (ApoE2, ApoE3 and ApoE4) that differ by 1 or 2 amino acids. Inheritance of the ApoE 4 allele is a risk factor for developing Alzheimer's disease (AD). The potential diagnostic value of ApoE protein levels in biological fluids (i.e. cerebrospinal fluid, plasma and serum) for distinguishing between AD patients and healthy elderly subjects is subject to great controversy. Although a re… Show more
“…Astrocyte-derived apoE is a separate pool from liver-derived apoE in the periphery (22) and is found at concentrations of ϳ5-10 g/ml in CSF and 50 g/ml in plasma (23). Peripheral apoE measured in plasma has previously been shown to decrease with APOE-⑀4 carrier status (23)(24)(25)(26). In the CNS, ELISA-based methods for estimating the relative or absolute amounts of apoE allelic isoforms have yielded conflicting results, possibly due to isoform-specific antibody preference and inherent variability of the assay.…”
"Human central nervous system (CNS) ApoE isoforms are increased by age, differentially altered by amyloidosis, and relative amounts reversed in the CNS compared with plasma."
“…Astrocyte-derived apoE is a separate pool from liver-derived apoE in the periphery (22) and is found at concentrations of ϳ5-10 g/ml in CSF and 50 g/ml in plasma (23). Peripheral apoE measured in plasma has previously been shown to decrease with APOE-⑀4 carrier status (23)(24)(25)(26). In the CNS, ELISA-based methods for estimating the relative or absolute amounts of apoE allelic isoforms have yielded conflicting results, possibly due to isoform-specific antibody preference and inherent variability of the assay.…”
"Human central nervous system (CNS) ApoE isoforms are increased by age, differentially altered by amyloidosis, and relative amounts reversed in the CNS compared with plasma."
“…In a similar fashion, a LC-MS assay for DcR3 and GDF15 was demonstrated to match reported immunoassays results but with higher resolution at low protein concentrations than antibody-based strategies and with the possibility of multiplexing [86]. Likewise, in recent years there has been a significant amount of published data on the quantitation of apolipoproteins using LC-MS [87][88][89][90][91][92][93]. Apolipoproteins are associated with the progression of cardiovascular and metabolic diseases, with apolipoprotein B100 and apolipoprotein A1 the primary components of low density lipoproteins (LDL) and high density lipoproteins (HDL), respectively.…”
Section: Lc-ms In Measurements Of Pharmacodynamic Proteinsmentioning
“…In order to evaluate the influence of matrix amount on signal, a labeled peptide (LGPLV*EQGR) was spiked at the same concentration in 100 L of water, serum or urine, respectively. LGPLV*EQGR peptide corresponds to the reporter peptide of the apolipoprotein E [40]. Spiked samples were submitted to enzymatic digestion and reconstituted in 200 L. The reconstituted samples were diluted with solvent (water or acetonitrile depending of chromatographic mode) before LC-MS/MS analysis.…”
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