The Role of Calcium Homeostasis in Axonal Spheroid Formation in Alzheimer’s Disease


Axonal spheroids (dystrophic neurites) associated with amyloid plaques are a significant hallmark of Alzheimer’s disease (AD). Our research has revealed that a single amyloid plaque can induce the development of spheroids in numerous adjacent axons. Using special imaging techniques, we’ve observed that these enlarged spheroids disrupt the flow of electrical signals in the brain, causing communication breakdowns between nerve cells. Excitingly, we’ve also discovered that spheroids might be reversible, potentially improving nerve cell communication and reducing network problems in AD patients, regardless of the amount of amyloid plaque present. In this study, we aim to delve deeper into understanding how spheroids grow and affect nerve cells by focusing on the potential role of cellular calcium levels in spheroid growth. Our research will use advanced imaging methods, proteomics and stem cell models to identify new targets for therapies that could help alleviate the harmful effects of axonal spheroids in AD, potentially complementing existing treatments targeting amyloid plaques.


Funding to Date



Studies of Alternative Neurodegenerative Pathways, Translational


Jaime Grutzendler, M.D.