It is our hope that the publication of our JAMA Neurology paper and the accompanying Alzforum story will motivate other laboratories to study Aβ*56. We certainly recognize that the existence of this species as an authentic oligomer that occurs in vivo is controversial. Perhaps, though, the following considerations will encourage skeptics and believers alike to take a closer look at Aβ*56.
The existence of specific Aβ oligomers as real entities, rather than artifacts, has been questioned because of the possibility that they are artificially generated through exposure to detergents, such as SDS. Several lines of evidence argue against this possibility.
1. When proteins in undiluted CSF are first separated by size-exclusion chromatography (SEC) and then analyzed by Western blot, Aβ*56 and Aβ monomers are seen in separate fractions eluted from the SEC column. If Aβ*56 was artifactually generated from monomers during the process of gel electrophoresis, one would expect to see both of these species in the same fractions from the SEC column.
2. Using the same extraction...