Dopamine Deficiency Drives Memory Impairment in Alzheimer’s Disease

Tohoku University Team Identifies a New Mechanism

A research team in Japan has found that the brain’s ability to form new associative memories depends on dopamine — and that this pathway breaks down early in Alzheimer’s disease.

Photo by Nikita Taparia on Unsplash

This article was originally published in Japanese on Ki to Oku. (Translated via Generative AI)

Dopamine and the Making of Memory

A joint research team led by Professor Kei Igarashi and Assistant Professor Tatsuki Nakagawa of Tohoku University, in collaboration with the University of California, Irvine, has found that dopamine levels drop sharply in the entorhinal cortex of Alzheimer’s disease model mice — and that this decline prevents the formation of associative memories. The team also showed that reactivating dopamine signaling, either through optogenetics or by administering levodopa, a drug widely used to treat Parkinson’s disease, restored memory function. The findings were published in Nature Neuroscience on April 23, 2026.

Dopamine is best known for its role in motivation and reward. But it plays an equally important part in how memories are formed. When you catch a scent, it often pulls up a place, a person, or a moment from the past — connecting one piece of experience to another. This is what researchers call associative memory, and it takes shape in the lateral entorhinal cortex, a region that serves as a gateway to the hippocampus. In 2021, Igarashi and colleagues reported in Nature that dopamine is essential to this process: released from dopamine-producing regions in the brainstem, it reaches the entorhinal cortex and encodes the link between a smell and what followed. The new study asked what happens to these dopamine-producing cells in Alzheimer’s disease.

When Dopamine Falls Short

The researchers used mice engineered to replicate the pathology of Alzheimer’s disease. In these animals, dopamine levels in the entorhinal cortex had fallen to less than one-fifth of normal, and neurons that would ordinarily respond to learned stimuli were no longer doing so.

The experimental setup was straightforward: two distinct scents were presented to the mice. If they chose one, they received sugar water; if they chose the other, a bitter liquid. Healthy mice learned to reliably distinguish between the two within about an hour. The Alzheimer’s model mice could not. The experiences were happening — the mice were smelling, tasting, living through each trial — but nothing was being laid down as memory.

What made the findings particularly striking was what remained intact. When tested on scents they had learned before the onset of disease, the Alzheimer’s model mice performed perfectly. They could still retrieve what they already knew. The dopamine deficit was not erasing the past; it was blocking the formation of anything new.

Reactivating dopamine input to the entorhinal cortex using light-based neural control restored associative memory formation. Administering levodopa produced the same effect, normalizing neural activity and recovering memory behavior in the mice.

Ki to Oku Perspective: The Past Remains

Alzheimer’s disease tends to be understood as a disease of forgetting — of memories dissolving, one by one, until little is left. This research complicates that picture.

In these experiments, the mice could no longer form new associations between a smell and its outcome. But the memories they had accumulated before the disease took hold were preserved in full. The capacity to recall the past remained unimpaired, even as the capacity to encode the present was slipping away.

What the Alzheimer’s model mice experienced was not erasure but blockage. Events occurred — smells, tastes, encounters — but without sufficient dopamine in the entorhinal cortex, those events could not be linked to other information and could not consolidate into lasting memory. The experience passed through; nothing stuck.

This distinction — between the formation of memory and the retrieval of it — offers a new lens for understanding how Alzheimer’s disease progresses, and where in that progression different capacities begin to fail.

Source: TOHOKU UNIVERSITY press release, Dopamine deficiency found to drive memory impairment in Alzheimer’s disease — UC Irvine News

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