Oligomeric amyloid β associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques

By Robert M. Koffie, Melanie Meyer‐Luehmann, T. Hashimoto, Kenneth W Adams, Matthew L. Mielke, M. Garcia-Alloza, Kristina D. Micheva, Stephen J. Smith, M. L. Kim, V. Lee and 2 more. Proceedings of the National Academy of Sciences of the United States of America, 2009

857 citations recorded by the source corpus.

Subfields: Cellular and Molecular Neuroscience, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/e2743dffdd3fd756e5313e4aa28b021c07aa8727

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Citations in the corpus

Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress Over the Last Decade. (2017, background): “The fibrils are, however, far from innocuous material, as they can deplete key components of the protein homeostasis network (81, 196), (as we discuss farther below in the section titled Protein Metastability and the Proteostasis Network), serve as a reservoir of protein oligomers that can be releas”
Alzheimer’s Disease and the β-Amyloid Peptide (2010, neutral): “While total abandonment of ﬁbril involvement in AD at this time is probably premature given the PIB story discussed earlier and the potential for plaque involvement with oligomer populations [91], the focus of the A β ﬁeld has shifted to soluble oligomers.”
Alzheimer's disease. (2011, background): “Although fibrillar Ab in mature AD plaques may contribute to neurotoxicity, such plaques are dynamic structures and likely act as local reservoirs of small, diffusible oligomers (Koffie et al. 2009).”
The amyloid state and its association with protein misfolding diseases (2014, background): “Paired betasheet structure of an Aβ(1-40) amyloid fibril revealed by electron microscopy.”
Molecular mechanisms of neurodegeneration in Alzheimer's disease. (2010, background): “A number of recent studies have begun to investigate the possibility that Ab oligomers might interfere with synaptic function by altering synaptic proteins such as post-synaptic density-95 [PSD95 (86– 89)], scaffold proteins such as Shank (90) and glutamate receptors (91).”
The amyloid hypothesis of Alzheimer's disease at 25 years (2016, background): “The latter findings fit nicely with evidence in hAPP tg mice that plaques in situ have a penumbra of soluble Ab oligomers in which synaptic density is low; synapse number rises toward normal the farther one measures from the edge of the plaque core (Koffie et al, 2009).”
Soluble amyloid β-protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration (2011, positive): “This result does not mean that plaques play no role in the fibrillary degeneration of neurons and their processes, as there is clear evidence that peri-plaque Aβ assemblies (type unspecified) are associated with local dendritic spine loss (33) and neuritic dystrophy in AD brains (34).”
Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012, background): “The abnormal NP-contacting dendrites and axons contain pathologic tau ﬁbrils identical to those seen in NFTs (244, 273), with loss of adjacent synapses (274, 275).”
Proliferation of amyloid-β42 aggregates occurs through a secondary nucleation mechanism (2013, background): “(2005) 3D structure of Alzheimer’s amyloid-beta(1-42) fibrils.”
Propagation of tau pathology in a model of early Alzheimer’s disease (2012, positive): “=3 at 21 months, 3 at 24 months old) mice and littermate controls (n=5 at 21 months, 3 at 24 months old) were prepared for array tomography as described previously (Koffie et al., 2009; Micheva and Smith, 2007).”