In Alzheimer’s disease, fibrous tau pathology accumulates and spreads in the brain, leading to synaptic loss. Researchers studying mouse models have found that tau protein can spread from presynaptic to postsynaptic synapses, and oligomeric tau protein has some synaptic toxicity. However, there is limited data on synaptic tau in the human brain. Recently, in a research report titled “Synaptic oligomeric tau in Alzheimer’s disease—a potential culprit in the spread of tau pathology through the brain,” published in the international journal Neuron, scientists from the University of Edinburgh and other institutions suggest that a deeper understanding of the spread mechanism of damaging proteins accumulated in Alzheimer’s disease patients’ brains may help develop new therapies to block the progression of this disease.
In the study, researchers discovered that synapses in the brain, responsible for transmitting basic signals, may also transport a toxic protein called tau. Tangles of tau protein, a hallmark feature of Alzheimer’s disease, form in brain cells, and when these tangles spread in the brain during the disease, the patient’s cognitive function declines. Researchers focused on studying synapses in the brain, which are crucial connections enabling the flow of chemical and electrical signals between brain cells. Alzheimer’s disease attacks synapses, and their loss strongly indicates a decline in memory and cognitive abilities.
In this study, researchers used powerful microscopy techniques to analyze over a million synapses and visually studied proteins within single synapses in 42 individual subjects. The results suggest that tau oligomers, protein aggregates of tau, may exist in the synapses of deceased Alzheimer’s disease patients. Researchers observed tau oligomer tangles at both ends of synapses, indicating the transfer of tau oligomers from signaling brain cells to receiving brain cells. In mouse models of Alzheimer’s disease, tau oligomers can jump from one side of the synapse to the other and spread toxic tau protein throughout the brain.
Researchers believe that reducing tau oligomers at synaptic sites may be a promising strategy to block disease progression. Alzheimer’s disease is the most common form of dementia, currently affecting 900,000 people’s health in the UK alone, and researchers predict this number will rise to nearly 1.6 million by 2040. The disease causes severe memory loss, and there is currently no effective cure. In conclusion, the study’s findings suggest that therapies targeting tau protein may offer a new approach to treating Alzheimer’s disease in humans in the future.