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S5‐03‐03: Linking molecular genetics and neuropathology at the MAPT locus
Author(s) -
WadeMartins Richard
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.2009.05.586
Subject(s) - locus (genetics) , biology , tau protein , neuropathology , genetics , exon , gene , alzheimer's disease , disease , medicine , pathology
the blood brain barrier. Activation of ApoE receptor-2 (Apoer2) by the neuromodulator Reelin enhances synaptic plasticity. Our objective was to investigate the interaction of ApoE, ApoE receptors and Abeta at the synapse. Methods: Electrophysiological measurements show that at the synapse Abeta depresses synaptic functions through mechanisms involving AMPA and NMDA receptors, while ApoE receptor increase NMDA receptor activity. Results: We now show that activation of ApoE receptors with a naturally occurring ligand can counteract the Abeta mediated synaptic depression over the physiological range of Abeta levels that are normally present in the CNS. This regulation is modulated in an isoform specific manner by ApoE. Conclusions: These findings suggest that the physiological functions of ApoE receptors and Abeta converge on the NMDA receptor at the level of the synapse, where both pathways countermodulate each other and thereby serve to maintain synaptic response within its optimal dynamic range.