Reduced Incidence of Dementia in Solid Organ Transplant Patients Treated with Calcineurin Inhibitors

Experimental evidence suggests that the protein phosphatase calcineurin mediates the action of amyloid-␤ (A␤) oligomers, the most toxic amyloid species thought to drive initial cognitive decline in Alzheimer's disease (AD).However, there is currently no evidence that inhibition of calcineurin could prevent the onset of AD in humans.Here, we report for the first time that individuals chronically treated with calcineurin inhibitors to prevent solid organ transplant rejection have a significantly lower incidence of AD/dementia as compared to the general population.This result prompts further clinical development of calcineurin inhibition as a viable treatment for AD.Keywords: Alzheimer's disease, calcineurin, dementia, FK506, solid organ transplant Alzheimer's disease (AD) is the most common ageassociated neurodegenerative disorder for which there is no resolving cure.Compelling evidence indicates that small soluble oligomers of amyloid-␤ (A␤) protein that precede senile plaque formation are the most toxic A␤ species in the AD brain [1,2], known to selectively target synaptic integrity and function [2][3][4][5][6].