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P1‐368: Monomeric and oligmeric Aβ assays on plasma of Alzheimer patients
Author(s) -
Xia Weiming,
Yang Ting,
Smith Imelda M.,
Walsh Dominic M.,
Selkoe Dennis J.
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.950
Subject(s) - monomer , proteolysis , chemistry , biomarker , alzheimer's disease , amyloid (mycology) , antibody , microbiology and biotechnology , biochemistry , medicine , immunology , biology , disease , enzyme , polymer , organic chemistry , inorganic chemistry
Background: Amyloid protein (A ), derived from proteolysis of APP, converts from monomeric form to oligomeric assemblies and eventually becomes the major component of the neuritic plaques. Besides its deposition in the central nervous system, A is also found freely circulating in blood, and quantitative measurement of systemic A has been actively explored as a biomarker for AD. In the past decade, levels of monomeric A in plasma have been quantified and associated with AD or propensity to AD. Methods: We employed sensitive sandwich ELISAs to measure monomeric A 40, monomeric A 42, and oligomeric A species in plasma samples obtained from 37 well-characterized AD patients and 10 agematched control subjects. Oligomeric A was measured by ELISA using the same N-terminal A antibody (82E1, Immuno-Biological Laboratories, Minneapolis, MN) for both capture and detection, and its specificity was validated by detecting covalently crosslinked synthetic A dimers. Results: We found that relative levels of monomeric A across all subjects were closely associated with their relative levels of oligomeric A . We obtained sequential blood samples from a subset of the AD patients and found a general decrease in plasma A 42 levels over a 1-2 year span. Nine of the 10 AD cases having sequential determinations showed a reduction in A -42 levels with time. In those patients who also had sequential determinations of A 1-42, most patients again showed a decrease over time. Most (9/10) control subjects had plasma levels of A 1-42 that were below the limit of detection of our ELISA for this species, whereas many (15/37) AD subjects had detectable A 1-42 levels by this assay, suggesting that a subset of our AD patients have elevated plasma A 1-42 levels. Similarly, oligomeric A ELISA showed a detectable signal in plasma in the same subset of AD patients. Conclusions: Although plasma A levels vary greatly among humans, we conclude that there is a trend to observe higher A 42 levels in plasma in at least a subset of AD versus control subjects and that A levels may decline over time in AD.