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P3‐235: Which cognitive function is influenced by vitamin D among older high‐functioning community‐dwellers?
Author(s) -
Annweiler Cedric,
Fantino Bruno,
Le Gall Didier,
Beauchet Olivier
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.2447
Subject(s) - cognition , polypharmacy , medicine , cognitive decline , confounding , effects of sleep deprivation on cognitive performance , episodic memory , trail making test , gerontology , cognitive test , demography , psychology , neuropsychology , disease , psychiatry , dementia , sociology
early events in Alzheimer disease. Specifically, it has been showed that Aß oligomers induce a decrease in dendritic spines, synaptic loss and plasticity alterations that underlie to the cognitive damage. However, the molecular mechanisms activated by Aß oligomers leading to synaptic dysfunction and loss, have not been completely explained. In our laboratory we described that Aß fibers induce c-Abl activation and regulates the neuronal death and cytoskeleton pathology. The c-Abl kinase is present in both pre and post synaptic structures and regulates the PSD-95 clustering. Besides has been described that the tyrosine kinase receptor ephrine A4 (EphA4) interacts with c-Abl and this interaction allows the reciprocal tyrosine phosphorylation. Methods: We treated wild type and EphA4-/hippocampal neurons (15 DIV) and synaptoneurosomes preparations with synthetic Aß42 oligomers and evaluated c-Abl and EphA4 signaling. Results: Here we show that c-Abl is involved in the synaptotoxicity induced by Aß oligomers. The Aß42 oligomers induce the c-Abl activation in dendritic spines of hippocampal neurons and in rat brain isolated synaptoneurosomes. Besides we observed that Aß42 oligomers increase the phospho tyrosine levels in EphA4 and the interaction between c-Abl and EphA4. Conclusions: Our data suggest Aß oligomers induce the c-Abl kinase activation through the EphA4 and this could be connected with synaptic demise.