Authors: Iryna Benilova, Eric Karran, & Bart De Strooper
This review paper excellently summarizes the experimental literature on Amyloid Beta’s (AB) role in precipitating the neurodegeneration that we associate with Alzheimer’s disease. Understanding AB’s role is complicated by the many AB species that exist, AB’s ability to aggregate/organize itself in different ways, the number of suggested mechanisms for its effects on the brain, and the generation of data from both in vivo and in vitro experiments. The title of the article refers to how some experimental literature pins the damaging effects of AB on a specific “toxic AB oligomer” (or specific set of oligomeric toxic AB species). The review’s authors explicitly, and implicitly through their discussion of the many potential mechanisms via which AB could play a role in the pathology of Alzheimer’s disease, implore their cohort to avoid accepting too quickly the hard-to-falsify, view-limiting hypothesis of the “toxic AB oligomer”.
Florida State University’s Computational Neuroscience group’s research relates to many of the findings presented in this paper. Some highlights were:
- “Further study of the synaptotoxic effects of AB… has shown disturbances in the functioning of postsynaptic NMDA receptors, affecting calcium influx, a number of downstream cascades and postsynaptic AMPA receptors.” – page 354
- Figure 4, which summarizes multiple avenues for AB-initiated neurodegenerative cascade, and thus illustrates that there is no consensus. – page 353
- “Interestingly, almost all AB oligomers show synaptotoxicity as measured by changes in dendritic spine morphology, altered long-term potentiation (LTP) and long-term depression (LTD) in hippocampal slices; effects on neurotransmission in cell culture; or defects in memory and cognition in rodents.” – page 351
- “… neurons in the vicinity of [amyloid] plaques display dystrophic neurites and synaptic loss, and elevated resting calcium levels are seen in neurons surrounding plaques in mouse models of Alzheimer’s disease.” – page 350