Quantification of modified amyloid beta peptides in Alzheimer disease and Down syndrome brains

Topic: Amyloid, tau and blood-test diagnosis

To gain insights into the different forms of modified amyloid beta peptides (A beta) in the Alzheimer disease (AD) and Down syndrome (DS) brain, we used two-site ELISAs with antibodies specific for isomerized (i.e. A beta with L-isoaspartate at positions 1 and 7) and pyroglutamate-modified (i.e. A beta beginning with pyroglutamate at position 3) forms of A beta to quantitate the levels of these different A beta peptides in formic acid extracts of AD and DS frontal cortex. Despite variations in the proportions of distinct forms of A beta in AD and DS frontal cortex, the major species of A beta in these samples were A betaN3(pyroGlu)-42 as well as A beta x-42 (where x is a residue at position 2 or less in A beta), whereas isomerized A beta was a minor species. Further, the levels of isomerized and pyroglutamate-modified forms of A beta terminating at amino acid 42 were higher than those ending at amino acid 40. The abundance of the distinct forms of A beta reported here in formic acid extracts of AD and DS frontal cortex suggests that these A beta species could play important roles in the deposition of A beta in AD and DS brains.

@article{hosoda1998-9825946,
  author  = {Hosoda, R. and Saido, T. C. and Otvos, L. and Arai, T. and Mann, D. M. and Lee, V. M. and Trojanowski, J. Q. and Iwatsubo, T.},
  title   = {{Quantification of modified amyloid beta peptides in Alzheimer disease and Down syndrome brains}},
  journal = {Journal of neuropathology and experimental neurology},
  year    = {1998},
  doi     = {10.1097/00005072-199811000-00012},
  pmid    = {9825946},
  url     = {https://doi.org/10.1097/00005072-199811000-00012}
}

Key findings

• The abundance of the distinct forms of A beta reported here in formic acid extracts of AD and DS frontal cortex suggests that these A beta species could play important roles in the deposition of A beta in AD and DS brains.

Why it matters

In formic acid extracts of frontal cortex from Alzheimer's disease and Down syndrome brains, the major amyloid-beta species were AbetaN3(pyroGlu)-42 and Abeta x-42, while isomerized amyloid-beta was a minor species. The authors suggest these distinct forms could play important roles in amyloid-beta deposition in both conditions.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1097/00005072-199811000-00012
• PubMed: 9825946
• Original source →
• Free full text: Journal of Neuropathology & Experimental Neurology →

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