Fig. 1.

The LEARn Models and Flint. LEARn explains idiopathic disorders in a testable manner, on the basis of accumulation of “hits” through an organism’s lifespan. Hits can be environmental, genetic, or epigenetic. A) An event such as a Pb/water exposure crisis would be the critical “initial hit” that sets up latent increased risk (red line) for late-life neurodegenerative disorders. As additional hits are received, people who had the primary hit progress to clinical neurodegeneration. People who did not have the critical early-life hit (un-exposed, dashed blue line) do not progress to disease, even though they also might bear later hits. B) The critical hit may occur before conception. Environmentally-induced epigenetic changes can be inherited, thus, even though individuals may be born after an acute “water crisis” has passed and suffer no direct exposure, the results of that exposure could still be passed on epigenetically and act as the critical primary hit (green line). C) In either case, appropriate remediation at an early enough interval may reverse epigenetic lesion in either primary-exposed individuals or their descendants (violet line). However, finding such lesions and appropriate remediation will require longitudinal research of affected individuals and their offspring.