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P4‐234: Aβ‐dependent inhibition of LTP in different intra‐cortical circuits of the visual cortex is mediated by RAGE
Author(s) -
Domenici Luciano,
Origlia Nicola,
Capsoni Simona,
Cattaneo Antonino,
Fang Fang,
Arancio Ottavio,
Yan Shi Du
Publication year - 2009
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.2009.04.700
Subject(s) - long term potentiation , entorhinal cortex , neuroscience , rage (emotion) , stimulation , cortex (anatomy) , chemistry , visual cortex , hippocampus , cerebral cortex , biology , receptor , biochemistry
oligomers or pretreatment with anti-Abeta antibodies were analyzed by immunoblot and immunohistochemistry. Results: Levels of oligomers detected with the A11 and 82E1 antibodies were correlated with the severity of the cognitive impairment (Blessed score and minimental) and with decrease in synaptic markers. Moreover, co-immunoprecipitation assays with frontal cortex of control and AD patients and mThy1-APP transgenic mice shows that compared to other synaptic proteins, an oligomerized recognizing antibody Abeta (82E1) interacts selectively with PSD95. Immunoblot, shows a reduction in the levels of the postsynaptic protein Shank1 and 3. In contrast, homogenates of AD patients or APP tg mice that were immunized with Abeta these effects were attenuated. Primary neuronal cultures were treated with conditioned media containing Abeta oligomers, in these preparations synaptic and dendritic spines were reduced, this was accompanied by a reduction in Shank3 levels. These effects can be blocked by pre-treatment with anti-Abeta antibodies. Conclusions: In conclusion, this study showed that the presence of a subpopulation of Abeta oligomers in the brains of patients with AD is predicts alterations in selected synaptic proteins and cognitive impairment and that this can be reversed by specific antibodies.