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article imageExplanation for why Alzheimer’s causes memory loss

By Tim Sandle     Oct 9, 2016 in Science
The tau protein has been implicated in Alzheimer’s disease. However, there has been, until now, little research about how then protein contributes to memory loss. A new theory has been proposed.
The aggregation of Tau protein has been linked in many studies to memory-related neurodegenerative disorders like Alzheimer’s disease. Understanding why this happens has been under-researched and little understood. Tau proteins are abundant in neurons of the central nervous system.
To overcome the knowledge gap in relation to the protein, scientists from the Gladstone Institute of Neurological Disease have produced a new study that shows how acetylated tau protein disrupts the neural machinery necessary for synaptic plasticity and memory performance.
To test out the theory, studies have been run using mice. For this, transgenic mice expressing human tau protein with mutations, designed to mimic increased tau acetylation observed in patients with severe Alzheimer’s disease were bred. With these mice, the tau was modified so that it became toxic and disrupted normal function.
The researchers ran studies to explor how tau triggers long-term potentiation (which affects the neuron related sites linked to learning and memory formation, within the hippocampus region of the brain.).
It was found from these studies that the mutant tau mice expressed impaired triggers long-term potentiation. This correlated with problems with spatial memory problems. More are details about the role of the tau protein are considered in a recent lecture from Professor Eckhard Mandelkow ("Role of Tau protein in Alzheimer Disease and neurodegenerative tauopathies"):
While evident through observational studies, the research did not explain what tau is doing after once it reaches specific postsynaptic sites. Digging deeper the researchers looked at a gene called KIBRA, which is associated with memory. Here differences in KIBRA expression are connected with variation in memory performance. Given that KIBRA-deficient mice have impaired long-term potentiation, a strong connection was evident and mutant tau appears to affect the expression of the memory formation related gene.
Lead researcher Dr. Tara Tracy told Biotechnqiues: “We found a link between acetylated tau and KIBRA, but we don’t really fully understand how tau is affecting KIBRA,” paving the way for additional studies.
The research to date has been published in the journal Neuron, with the study titled “Acetylated tau obstructs KIBRA-mediated signaling in synaptic plasticity and promotes tauopathy-related memory loss.”
More about Alzheimer's disease, tau protein, Memory, Neurodegenrative disease
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