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Neurobiological Mechanisms of Memory Loss in Alzheimer's Disease

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Studying the underlying causes of memory loss

Alzheimer's disease is the leading cause of dementia. It presents an enormous medical, social, and economic challenge to Europe.

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To address this problem, the 'Neurobiological mechanisms of memory loss in Alzheimer's disease' (MEMOLOAD) project focused on the molecular and biological mechanisms underlying memory loss. There is growing evidence that amyloid-beta peptide (Abeta) causes memory loss by directly or indirectly interacting with the signalling pathways involved in memory consolidation. A consortium of the seven best available research groups worked together to identify at the molecular level how accumulation of Abeta impairs the flexibility, or plasticity, of brain synapses that results in memory loss. Secondly, the consortium is developing new peptidomimetric molecules that disrupt Abeta proliferation. Researchers began by developing behavioural tasks sensitive to small changes in synaptic signalling and plasticity in the cerebral cortex and hippocampus. All participating laboratories then used these tasks to test the success of drug treatments on Abeta production in transgenic mouse models. Next, the research focus switched from Abeta-induced changes in individual synapses to the impact on large neuronal populations and the entire neural network. Second, acute effects of Abeta on synaptic plasticity were compared to long-term changes in the brain. Finally, brain activity in rodents was measured as they performed a memory task to track changes in network communication. Other experiments aimed at determining the direct and indirect effects of Abeta on two signalling pathways central to memory consolidation, developing synthetic Abeta compounds to be used for further study. The team also synthesised peptides to determine if they inhibit Abeta growth. While these peptides have not proven to be effective, scientists are continuing to look for other compounds. This research has contributed significantly to understanding of brain memory mechanisms. The consortium also has added research tools, including new animal models for testing and imaging methods to screen for Abeta-induced changes. Over time, the hope is to find an effective therapy to halt the disease's progression.

Keywords

Alzheimer's disease, memory loss, amyloid-beta peptide, Abeta, memory consolidation, signalling pathways

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