Quantification of Modified Amyloid β Peptides in Alzheimer Disease and Down Syndrome Brains

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To gain insights into the different forms of modified amyloid β peptides (Aβ) in the Alzheimer disease (AD) and Down syndrome (DS) brain, we used two-site ELISAs with antibodies specific for isomerized (i.e. Aβ with L-isoaspartate at positions 1 and 7) and pyroglutamate-modified (i.e. Aβ beginning with pyroglutamate at position 3) forms of Aβ to quantitate the levels of these different Aβ peptides in formic acid extracts of AD and DS frontal cortex. Despite variations in the proportions of distinct forms of Aβ in AD and DS frontal cortex, the major species of Aβ in these samples were AβN3(pyroGlu)-42 as well as Apx-42 (where x is a residue at position 2 or less in Aβ), whereas isomerized Aβ was a minor species. Further, the levels of isomerized and pyroglutamate-modified forms of Aβ terminating at amino acid 42 were higher than those ending at amino acid 40. The abundance of the distinct forms of Aβ reported here in formic acid extracts of AD and DS frontal cortex suggests that these Aβ species could play important roles in the deposition of Aβ in AD and DS brains.

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