A new lens on Alzheimer's disease: Insights into the Edinger-Westphal nucleus and its circuits

Alzheimer's disease (AD) is the primary cause of dementia, and as the population ages, the number of individuals affected by the disease continues to rise. However, effective treatments for AD are still lacking. In the initial stages of AD, many brain regions are susceptible to its characteristic pathological changes, such as the Edinger-Westphal nucleus (EW nucleus) located in the midbrain region, which functions primarily as the parasympathetic oculomotor nucleus regulating pupil constriction. In this review, we outline the characteristics of EW nucleus alterations in AD and their potential role in the disease's onset and progression from various perspectives, including molecular changes, pathological alterations, and synaptic circuits. We propose that cognitive functions governed by the EW nucleus and its associated circuits may undergo early changes in AD and could serve as potential targets for the early diagnosis and therapeutic development of AD.