Dopamine circuit disruption in Alzheimer’s disease

Although it is well known that the brain area for memory formation, entorhinal cortex alterations is involved in Alzheimer’s disease (AD),   the circuit mechanisms causing its selective vulnerability is not well understood.

The authors in this study dhow that the dopamine neurons projecting their axons to the lateral entorhinal cortex (LEC), critical for memory formation in healthy brains, become dysfunctional from the early pathological stage and cause associative memory impairments in amyloid precursor protein knock-in mice.

LEC dopamine fibers associative learning behavior rescued after optogenetic reactivation and L-DOPA treatment in amyloid precursor protein knock-in mice indicating early dysfunction of LEC-projecting dopamine neurons underlie memory impairment in AD from early stages.

https://www.nature.com/articles/s41593-026-02260-w

https://sciencemission.com/dopamine-disruption-in-the-entorhinal-cortex