ObjectiveSeveral studies have reported that non-demented older adults with clinical depression show changes in amyloid- (A) levels in blood, cerebrospinal fluid and on neuroimaging that are consistent with those observed in patients with Alzheimer's disease. These findings suggest that A may be one of the mechanisms underlying the relation between the two conditions. We sought to determine the relation between elevated cerebral A and the presence of depression across a 54-month prospective observation period. MethodsCognitively normal older adults from the Australian Imaging Biomarkers and Lifestyle study who were not depressed and had undergone a positron emission tomography scan to classify them as either high A (n=81) or low A (n=278) participated. Depressive symptoms were assessed using the Geriatric Depression Scale Short Form at 18-month intervals over 54months. ResultsWhilst there was no difference in probable depression between groups at baseline, incidence was 4.5 (95% confidence interval [CI] 1.3-16.4) times greater within the high A group (9%) than the low A group (2%) by the 54-month assessment. ConclusionsResults of this study suggest that elevated A levels are associated with a 4.5-fold increased likelihood of developing clinically significant depressive symptoms on follow-up in preclinical Alzheimer's disease. This underscores the importance of assessing, monitoring and treating depressive symptoms in older adults with elevated A. Copyright (c) 2016 John Wiley & Sons, Ltd.