Alzheimer’s disease is undergoing a paradigm shift in management. Building on the first ever evidence in 2021 that effective disease modifying therapies are possible, anti-amyloid drugs have been approved for use in people with mild cognitive impairment in several countries, including Australia. Such drugs are most effective when delivered in the earliest stages of the disease. The drive now is to develop improved diagnostic strategies capable of both “ruling in” people who are excellent candidates for therapy and “rule out” those who do not need treatment.

International attention has focused on blood-based biomarkers capable of reflecting the defining neuropathological feature of Alzheimer’s disease, accumulation of extracellular amyloid-b plaques. Yet amyloid load does not always correlate with cognitive decline. Indeed, sporadic Alzheimer’s disease results from a combination of lifestyle, environmental, and genetic influences. This suggests that additional biomarkers may be required.

MicroRNA are a class of regulatory RNA that coordinate the expression of functionally related genes, including those involved in cognition and a wide range of neuronal functions, which are dysregulated in Alzheimer’s disease. Critically, from a biomarker standpoint, microRNA are stable in plasma and can be detected by routine technologies already available in diagnostic laboratories.

This seminar will focus on the discovery of a panel of plasma miRNA which are altered in people at high risk of developing Alzheimer’s disease and show that this panel provides a strong balance between diagnostic accuracy and model simplicity, achieving an AUC of 0.990, sensitivity 94%, specificity 96%, classification accuracy of 94%. As this model was validated in additional cohorts and was effectively able to distinguish amyloid converters (AUC of 0.928), it may be a uniquely informative disease monitoring tool that could enhance molecular diagnosis of AD.