Shear-Induced Amyloid Formation in the Brain: IV. Effects on Synapses Surrounding Senile Plaque and in Plaque-Free Regions
| Autor: | Conrad N. Trumbore |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Amyloid Synaptic cleft Neuron membrane Plaque Amyloid amyloid-β Synapse prion 03 medical and health sciences 0302 clinical medicine Interstitial fluid Postsynaptic potential synapse Animals Humans Senile plaques oligomers Chemistry shear energy General Neuroscience Brain General Medicine Amyloidosis Hypothesis synaptic cleft Psychiatry and Mental health Clinical Psychology 030104 developmental biology Shear (geology) Synapses Biophysics Geriatrics and Gerontology Shear flow Shear Strength 030217 neurology & neurosurgery seeding |
| Zdroj: | Journal of Alzheimer's Disease |
| ISSN: | 1875-8908 1387-2877 |
| Popis: | Amyloid-β oligomers (AβO) have been proposed as neurotoxins in the synaptic dysfunction that precedes Alzheimer's disease symptoms. Human and animal model studies report that senile plaques contain a halo of AβO molecules surrounding these plaques. A far smaller number of oligomers are distributed widely in plaque-free regions. It has been suggested that oligomers migrate from halos to nearby synapses and are incorporated into both pre- and postsynaptic terminals. These two types of oligomers have two different toxicities when extracted and injected in animal models. This paper proposes a shear-energy based explanation for the data in these studies. Shear hypotheses in the preceding three papers in this series are applied to suggest how the hydrodynamics and resulting shear patterns explain the spatial distribution of both AβO types, the apparent synapse loss in the vicinity of plaque particles, and possible reasons for the differing toxicities. A shear-based mechanism is proposed for the preferential migration of locally shear-excited Aβ molecules into the synaptic cleft. It is proposed that high energy laminar shear generated by the forced diversion of interstitial fluid around the flow-impeding plaque particle is responsible for the formation of AβOs around the plaque. It is suggested that in plaque-free regions, a different type of AβO with different toxicity is generated by lower energy shear flow around synapses, depositing AβO within the synapse from either the neuron membrane surface or by prion-like seeding within the synaptic cleft by locally-sheared Aβ molecules near the synapse entry. |
| Databáze: | OpenAIRE |
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