The remarkable properties of amyloid-β derived from human Alzheimer's disease brain: swinging the streetlight.

Abstract

This scientific commentary refers to ‘Highly potent soluble amyloid-β seeds in human Alzheimer brain but not cerebrospinal fluid’ by Fritschi et al. (doi: 10.1093/brain/awu255). Despite many years of intensive study, the specific amyloid-β species in the human brain responsible for the pathophysiological processes underlying Alzheimer’s disease have yet to be identified. In part, this may be because we have been ‘searching under the streetlight’: examination of other sources of amyloid-β such as synthetic preparations, material derived from the brains of transgenic animals, and amyloid-β recovered from human CSF after lumbar puncture has been much more convenient than direct evaluation of human brain-derived material. However, telltale signs over the last several years have indicated that amyloid-β derived from human brain may have properties or constituents that are qualitatively and quantitatively different from those of amyloid-β from other sources. The paper by Fritschi et al. (2014) from Mathias Jucker’s group in this issue of Brain is a major contribution to this line of investigation. Notably, the paper provides perhaps the most definitive evidence yet that human brain-derived amyloid-β has fundamentally dissimilar properties to human CSF-derived material. Specifically, Fritschi et al. demonstrate that <1 …