P008 - DEFICIENT COGNITIVE AND EMOTIONAL FUNCTIONS AND NEUROTRANSMITTER LEVELS IN THE TGDIMER MOUSE THAT EXPRESSES AMYLOID-BETA DIMERS, BUT NO PLAQUE PATHOLOGY (ID 2152)
Abstract
Aims
Soluble amyloid-beta oligomer has been recently implicated as a critical pathogenic feature in Alzheimer's disease (AD), preceding the significant amyloid beta-peptide aggregation. Different forms of soluble amyloid-beta species are associated with synaptotoxicity and gradual escalation of the clinical progression. Although the exact underlying mechanism is still poorly understood, it leads to the known early Alzheimer's synaptic dysfunction, learning and memory deterioration.
Methods
A novel genetically modified "tgDimer" mouse, with reliable production of high amount of a single soluble amyloid-beta oligomer "dimer" is investigated. Evidence was obtained for its age-related impact on spatial learning, attention, spatial memory synaptic-plasticity and neurochemistry balance. In this study, together with a further detailed neurochemical characterization of the "tgDimer" mouse by high-performance liquid chromatography, a comprehensive battery of behavioral tests are carried out to assess dysfunction of region-specific learning and memory formation and emotional behaviors.
Results
Our results suggest that amyloid-beta dimer; in the absence of insoluble aggregates, plays a significant role in causing deficits in reference, but not working spatial memory, resistance to extinction, reward-motivated learning, cognitive flexibility, temporal order memory (what and when), and higher-order memories (episodic-like memory). Furthermore, amyloid-beta dimer influences affective symptoms as hyponeophagia and anhedonia reminiscent of early AD and the balance of neurotransmitter systems.
Conclusions
The tgDimer mouse allows a more specific description of behavioral phenotypes in early AD, where therapeutic approaches are more likely to be effective before the massive structural changes occur. We conclude that amyloid-beta dimers contribute to neurotransmitter dysfunction and behavioral impairments, characteristic of the early stages of AD.
