Accumulation of Tau Protein and Alzheimers Disease Link Established

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In addition to an accumulation of amyloid which causes characteristic plaques to occur in the brain of Alzheimer’s patients, a buildup of another protein called tau has been established as another biomarker for detection of the disease. Researchers at the University of Minnesota have confirmed the protein buildup in the dendritic spines as a cause of communication disruption between brain cells and subsequent memory loss.

Accumulation of Tau Occurs Early in Alzheimer's Disease, Before Symptoms

Tau proteins are abundant in neurons in the central nervous system and stabilize microtubules, a component of the cytoskeleton. When tau proteins are defective, they accumulate abnormally into clumps of neuron-damaging deposits that disrupt neuronal communication at the synapses.

“Research has shown that healthy neurons have more tau in the axon and less in the cell body and dendrites, and that this gradient is reversed in neurodegenerative disorders like Alzheimer’s,” says study author Dr. Karen H. Ashe, a neuroscientist at the university’s Ashe Laboratory. She and co-author Dr. Dezhi Liao aimed to find how tau diminishes brain function in the preclinical stages of the disease.

Read: Biomarkers Promising for Identifying Alzheimer's Disease

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The researchers found that aggregates of tau sometimes have multiple phosphate groups attached, called hyperphosphorylated tau, which caused a “mislocalization” of the cells, subsequently impairing the synapses. Once these are mislocalized, tau suppresses excitatory synaptic transmission and cause a loss of surface AMPA receptors in the spines.

“These findings capture what is likely the earliest synaptic dysfunction that precedes synapse loss in tauopathies and provide an important mechanistic link between tau phosphorylation and the misclocalization of tau to dendritic spines,” concludes Dr. Liao.

While most treatments in clinical studies for Alzheimer’s currently are focused on reducing amyloid plaques, the U-M study was designed to show how tau also impacts the decline of brain functioning.

Read: Detecting Alzheimer's Early, Is It Possible?

“Ever since Alois Alzheimer described the plaques and tangles that were evident when he examined the brains of demented patients in 1906, the focus of scientific research on Alzheimer’s disease has been on these plaques and tangles,” says Ashe. “Our discoveries have been helpful in shifting prevailing thought: Plaques and tangles are now considered late stage lesions of the disease, not the causes of it.”

Earlier this year, the University of Minnesota won a $4.3 million grant from the National Institutes of Health to study potential causes of Alzheimer’s disease. The researchers believe that there is not one root cause of Alzheimer’s, but a combination of physiological factors.

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