Untangling the role of tau in Alzheimer’s disease: A study has revealed how tau — a key protein implicated in Alzheimer’s disease — impairs communication between neurons, providing new avenues for treatment
Alzheimer’s disease is a brain disorder that causes neurons to die, slowly destroying memory and thinking skills. It’s the most common type of dementia, impacting an estimated 50 million people worldwide. Despite its prevalence, the causes remain poorly understood and treatment options are limited.
Now, a team of scientists in Japan has revealed how excess tau — a key protein implicated in Alzheimer’s disease — impairs signaling between neurons in the brains of mice. The study, published recently in eLife, could open new pathways for treating the symptoms and even halting the progression of Alzheimer’s disease and other neurodegenerative disorders.
Tau is produced in neurons, where it binds to and promotes the assembly of microtubules — long, thin filaments that maintain cell structure and provide pathways for transport within the cell. Tau usually exists in either this bound state, or it is dissolved in the liquid that fills the cell.
However, in some neurological disorders, most famously in Alzheimer’s disease, levels of soluble tau in certain brain regions become too high, and it aggregates into insoluble structures called neurofibrillary tangles.
“A lot of scientists focus on the impact of these visible neurofibrillary tangles that are a hallmark of Alzheimer’s, but actually, it’s the invisible levels of soluble tau that correlate most closely with cognitive decline,” said Professor Tomoyuki Takahashi, senior author of the study, and head of the Cellular and Molecular Synaptic Function Unit at OIST.
The research began ten years ago, when his team looked at the effect of high levels of soluble tau on signal transmission at the calyx of Held — the largest synapse in mammalian brains. Synapses are the places where two neurons make contact and communicate. When an electrical signal arrives at the end of a presynaptic neuron, chemical messengers, known as neurotransmitters, are released from membrane ‘packets’ called vesicles into the gap between neurons. When the neurotransmitters reach the postsynaptic neuron, they trigger a new electrical signal.
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