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P4‐261: The effects of low concentrations of the beta‐amyloid peptide at the hippocampal synapse
Author(s) -
Russell Claire,
Empson Ruth,
Austen Brian,
Alifragis Pavlos
Publication year - 2008
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.2008.05.2330
Subject(s) - hippocampal formation , schaffer collateral , long term potentiation , neuroscience , synaptic plasticity , synapse , hippocampus , amyloid beta , chemistry , biology , peptide , receptor , biochemistry
the relation between A 42 accumulation and microtubule-associated protein pathologies. Immunohistochemistry, including dual-labeling immunoEM, and biochemical methods are used to examine alterations in tau and MAP2 in relation to A 42 accumulation in neurons of AD transgenic mouse models in vivo with aging and in vitro with time in culture. Live cell imaging is used to study transport in cultured neurons. Results: We provide the first ultrastructural evidence that localized intraneuronal accumulation of A 42 is spatially associated with the initiation of aberrant tau phosphorylation and reduction in microtubule-associated protein 2 (MAP2) within synaptic compartments of neurons in brains of AD transgenic mice. We previously observed early, selective and progressive alterations in synaptic proteins in A 42 accumulating APP mutant neurons with time in culture and are examining whether changes in MAPs (tau and MAP2) precede these changes. Since alterations in MAPs can alter neuronal transport, and because A 42 and internalized EGF localize to late endosomes, we are also examining transport of EGF-labeled vesicles in APP mutant compared to wild type neurons in culture; our results support early transport alterations of late endosomes in neurites of Tg2576 neurons in culture. Conclusions: We will provide the first data linking A and tau alterations to early synaptic pathology in transgenic mouse models of AD and present data on alterations in MAPs in relation to changes in synaptic proteins and vesicular transport in A accumulating neurons with time in culture.