PSP, like Alzheimer's disease (AD), is a tauopathy. The etiopathogenesis of PSP is not well known and the role of stress has not yet been examined. Recent studies have shown that stress increases the risk for developing AD. This study investigates the role of stress as a risk factor for PSP.B To examine the association between the development of progressive supranuclear palsy (PSP) and self-reported life stressors.76 patients diagnosed with PSP according to the NINDS-SPSP criteria and 68 age-matched unrelated controls were administered a life stressor questionnaire. Stress was quantified as total number of events, number of life changing events, and number of events characterized by self-rated severity. Conditional odds ratio (OR) was calculated for each measure, with participants in the highest quartile of each measure being defined as high-exposure in relation to all other participants.There were no significant differences between the reported number of total events or life-changing events in cases and controls. However, we found 24.4% of cases (N = 11) and 9.1% of controls (N = 5) had a higher exposure to high severity events, yielding an OR of 3.2 (p = 0.04).We found that cases have over a three times greater odds of high exposure to high-severity events than controls prior to the clinical development of PSP, while there were no differences in overall number of reported events. Our findings suggest that high exposure to highly stressful events may be associated with the development of PSP.