It is estimated that fewer than ten percent of Alzheimer’s Disease cases have a genetic basis, with the factors that contribute to the rest of the cases remaining largely unknown. Following up on epidemiological studies, scientists at the Max Planck Institute of Psychiatry hypothesized that adverse life events (stress) may be one trigger of Alzheimer's disease.  Ioannis Sotiropoulos, from the  Max Planck Institute of Psychiatry (Germany), and colleagues found increased hyperphosphorylation of tau protein in the hippocampus and prefrontal cortex of rats that has been subjected to stress (such as overcrowding, placement on a vibrating platform, etc.) for one hour daily over a period of one month. Animals showing these changes in tau also showed deficits in memories that depended on an intact hippocampus; also, animals with abnormally hyperphosphorylated tau were impaired in behavioral flexibility, a function that requires proper functioning of the prefrontal cortex. These results complement previous demonstrations by the scientists that stress leads to the formation of beta-amyloid, another protein implicated in Alzheimer's disease. Observing that: “Many [Alzheimer’s Disease] patients hypersecrete glucocorticoids (GCs), and their GC levels correlate with the rate of cognitive impairment and extent of neuronal atrophy,” the researchers conclude that: “Lifetime stress/[glucocorticoids] exposure may have a cumulative impact on the onset and progress of [Alzheimer’s Disease] pathology, with TAU hyperphosphorylation serving to transduce the negative effects of stress and [glucocorticoids] on cognition.”