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Urea‐based two‐dimensional electrophoresis of beta‐amyloid peptides in human plasma: Evidence for novel Aβ species
Author(s) -
Maler Juan Manuel,
Klafki HansWolfgang,
Paul Sabine,
Spitzer Philipp,
Groemer Teja Wolfgang,
Henkel Andreas Wolfram,
Esselmann Hermann,
Lewczuk Piotr,
Kornhuber Johannes,
Wiltfang Jens
Publication year - 2007
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200700311
Subject(s) - peptide , cerebrospinal fluid , human plasma , chemistry , amyloid (mycology) , gel electrophoresis , urea , biochemistry , microbiology and biotechnology , biology , chromatography , neuroscience , inorganic chemistry
The detailed analysis of β‐amyloid (Aβ) peptides in human plasma is still hampered by the limited sensitivity of available mass spectrometric methods and the lack of appropiate ELISAs to measure Aβ peptides other than Aβ 1–38 , Aβ 1–40 , and Aβ 1–42 . By combining high‐yield Aβ immuno precipitation (IP), IEF, and urea‐based Aβ‐SDS‐PAGE‐immunoblot, at least 30 Aβ‐immunoreactive spots were detected in human plasma samples as small as 1.6 mL. This approach clearly resolved Aβ peptides Aβ 1–40 , Aβ 1‐42 , Aβ 1‐37 , Aβ 1‐38 , Aβ 1‐39 , the N‐truncated Aβ 2–40 , Aβ 2–42 , and, for the first time, also Aβ 1–41 . Relative quantification indicated that Aβ 1–40 and Aβ 1–42 accounted for less than 60% of the total amount of Aβ peptides in plasma. All other Aβ peptides appear to be either C‐terminally or N‐terminally truncated forms or as yet uncharacterized Aβ species which migrated as trains of spots with distinct p I s. The Aβ pattern found in cerebrospinal fluid (CSF) was substantially less complex. This sensitive method (2‐D Aβ‐WIB) might help clarifying the origin of distinct Aβ species from different tissues, cell types, or intracellular pools as well as their amyloidogenicity. It might further help identifying plasma Aβ species suitable as biomarkers for the diagnosis of Alzheimer's disease (AD).