AsianScientist (Jun. 29, 2026) – For decades, Alzheimer’s disease research has largely focused on the accumulation of amyloid-β plaques and tau tangles in the brain. Yet therapies targeting these hallmark features have had little success in restoring memory. Now, researchers have uncovered another important piece of the puzzle: dopamine deficiency.
Researchers from Tohoku University in Japan, and the University of California, Irvine, have recently identified dopamine dysfunction as a previously unrecognised mechanism underlying memory impairment. Their findings, published in Nature Neuroscience, suggest that restoring dopamine activity could become a promising strategy for treating cognitive decline in Alzheimer’s patients across the globe.
Memory formation is often associated with experiences. A certain smell can evoke memories from childhood, or a song on the radio can make us recall an event from the past. While scientists have long known that the medial temporal lobe lies at the heart of memory formation, they have struggled to understand the neural changes that disrupt this process in Alzheimer’s disease.
To investigate this, a research team led by Kei Igarashi, a Distinguished Professor at Tohoku University School of Medicine, focused on the entorhinal cortex, a brain region that serves as the gateway to the hippocampus, which is essential for learning and memory.
Previous studies had shown that dopamine plays a crucial role in forming memories in this region. The team wanted to determine whether disruptions in dopamine signalling contribute to the memory deficits seen in Alzheimer’s disease.
Restoring dopamine restores memory
Using a mouse model of Alzheimer’s disease, the researchers found that dopamine levels in the entorhinal cortex had dropped to less than 20 per cent of normal levels. This reduction was accompanied by severe impairments in associative memory, which were observed during odor-based learning tasks.
Electrophysiological analyses further revealed that neurons in this region failed to respond appropriately to stimuli that should be encoded as memories.
The team then investigated whether restoring dopamine in the entorhinal cortex could reverse these deficits.
Using optogenetic techniques, they increased dopamine release in the affected brain region, and found that this intervention restored the mice’s ability to form memories.
The researchers also tested Levodopa, a drug commonly prescribed for Parkinson’s disease that increases dopamine levels in the brain. It normalised neural activity in the entorhinal cortex and significantly improved memory performance in the mice.
“We revealed that dopamine dysfunction plays a central role in memory impairment in Alzheimer’s disease,” explained Kei Igarashi. “The discovery was unexpected, but it opens new possibilities for therapeutic intervention for the millions of Alzheimer’s disease sufferers around the world.”
The findings from this study show that dopamine is a critical component of memory circuits, and that targeted interventions to restore dopamine signaling may help slow or reverse cognitive decline.
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Source: Tohoku University School of Medicine ; Image: atlascompany/Magnific
The study can be found at : Early dopamine disruption in the entorhinal cortex of a knock-in model of Alzheimer’s disease
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