Alzheimer's Disease Is a Synaptic Failure

By D. Selkoe. Science, 2002

4,348 citations recorded by the source corpus.

Subfields: Cellular and Molecular Neuroscience, Computational Theory and Mathematics, Physiology

View Paper: https://www.semanticscholar.org/paper/b31e45f340ef52735be6ac2aeda5a20bf7922fdf

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Citations in the corpus

Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior. (2008, background): “…and cognitive analyses provided the first direct behavioral data supporting the emerging hypothesis that diffusible oligomers of Aβ are responsible for important components of neuronal dysfunction leading up to or associated with AD (reviewed in Klein et al. 2001; Selkoe 2002; Walsh et al. 2003).”
Neurodegenerative diseases target large-scale human brain networks (2009, background): “Synapses falter, and damage spreads to new regions, accompanied by worsening clinical deficits (Selkoe, 2002).”
Effects of secreted oligomers of amyloid β‐protein on hippocampal synaptic plasticity: a potent role for trimers (2006, background): “The amyloid (or Aβ) cascade hypothesis proposes that the abnormal accumulation of Aβ inhibits synaptic function, gradually induces neuritic and glial changes, and initiates a process of neurodegeneration (Hardy & Selkoe, 2002).”
Inhibition of mTOR by Rapamycin Abolishes Cognitive Deficits and Reduces Amyloid-β Levels in a Mouse Model of Alzheimer's Disease (2010, background): “ative disorder in the elderly[8], is currently without effective”
Dendritic spine pathology in neuropsychiatric disorders (2011, background): “Although Alzheimer's disease is a definitive neurodegenerative disease, much evidence supports synaptic dysfunction as a preceding and contributing insult to eventual neuronal deat”
Immune modulation of learning, memory, neural plasticity and neurogenesis. (2011, neutral): “and neurodegeneration, an even greater impairment in neurobehavioral plasticity ensues (Selkoe, 2002).”
Natural oligomers of the amyloid-β protein specifically disrupt cognitive function (2005, background): “β-amyloid(1-40) effects on behavior and memory.”
Prediction of "aggregation-prone" and "aggregation-susceptible" regions in proteins associated with neurodegenerative diseases. (2005, methodology): “Alzheimer’s disease is a neurological disorder characterised by the progressive deposition in the brain of the Ab40 or the Ab42 peptide.(9) Since the location, and hence the local pH, at which the aggregation process leading to such deposition occurs in vivo is not known precisely, we used equations”
Regulation of NMDA receptor trafficking by amyloid-β (2005, background): “Soluble extracellular amyloid-β may initiate memory impairments before the accumulation of plaque”
The complement system: an unexpected role in synaptic pruning during development and disease. (2012, background): “However, it has recently emerged that neuron death is preceded by aberrant synaptic functioning and massive synapse loss (Selkoe 2002, Mallucci 2009).”
Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy (2009, background): “APOE, synaptic plasticity and spine integrity Synaptic failure is an early pathological feature of A”
Synaptic Targeting by Alzheimer's-Related Amyloid β Oligomers (2004, background): “Alzheimer’s disease (AD) is a progressive dementia that manifests in early stages primarily as a profound inability to form new memories (Selkoe, 2002).”
Hallmarks of neurodegenerative diseases. (2023, neutral): “…nuclear, cytoplasmic, and pre-or post-synaptic), enabling their interference with different NDD hallmarks (outlined below), 7,10,12,14,19,21,22,24,25,27,44,64–67 (Figures 1 and 3), although the exact toxic mechanism and the toxic forms of these aggregates have not yet been unequivocally deﬁned.”
Amyloid-β and tau — a toxic pas de deux in Alzheimer's disease (2011, background): “, and loss of synapses is one of the earliest events that has been associated with functional impairmen”
Experience-dependent structural synaptic plasticity in the mammalian brain (2009, background): “Spines in disease and injury Synaptic dysfunction is one of the first hallmarks of neurodegenerative diseas”