Fig. 1

The lifelong journey of a healthy brain into AD and brain organ failure. The factors that contribute to the development, and alter risk for, AD are depicted below a hypothetical lifespan of someone who gets symptomatic AD at 80 years of age. The blue coloring indicates the time and strength of those factors that are active or emerge variably during the lifespan. Pathology onset begins some 25–30 years before symptoms emerge and shows a characteristic sequence of changes beginning with Aβ deposition followed by cellular dysfunction, tau pathology and neurodegeneration. Age related co-morbidities can have increasing impact on disease course in late life. Brain and cognitive reserve can alter symptom emergence and progression without altering underlying pathology