15 October 1999. From today's Journal of Neuroscience comes evidence that intermediate Aβ species could be damaging neurons. Dean Hartley, Dennis Selkoe, and their colleagues report that so-called
"protofibrillar" Aβ (oligomers intermediate between Aβ monomers and amyloid fibrils) can induce electrophysiological changes and progressive toxicity in cortical neurons.
In mixed (neuronal and glial) cultures from embryonic rat neocortex, the
addition of either low-molecular-weight (mainly monomeric) Aβ or
protofibrils induced toxicity in a time- and concentration-dependent
manner, despite the fact that there was no detectable formation of
mature amyloid fibrils during this time. Protofibrils, but not low-molecular-weight Aβ, also induced electrophysiological changes (increased EPSPs, action potentials, and membrane depolarizations) in cultured neurons.
Based on this evidence that protofibrils have biologic, and toxic, activity, the authors suggest the possibility that "the preclinical and early clinical progression of AD is driven in part by the accumulation of specific Aβ assembly intermediates...." The role of protofibrillar Aβ in human Alzheimer disease pathogenesis remains to be determined.-Hakon Heimer.
Hartley DM, Walsh DM, Chianping PY, et al. Protofibrillar intermediates of amyloid-β protein induce acute electrophysiological changes and progressive neurotoxicity in cortical neurons. J Neurosci 1999;19(20). Abstract