Neurodegenerative diseases (NDs), including AD/FTD/PD, may begin with prolonged asymptomatic stages and present with similar clinical manifestations in early stages. While early stages of different NDs affect different brain regions and are likely triggered by distinct pathophysiological mechanisms, most NDs are characterized by early synaptic dysfunction/loss. 

DiamiR developed a platform technology for early detection, differential diagnosis, and prognosis of AD and other NDs based on targeted selection and quantitative analysis of synapse/brain-enriched microRNAs circulating in plasma. microRNAs are small non-coding regulatory molecules whose levels change in disease; some microRNAs are specific to or enriched in the brain, appear in extracellular space, and cross the blood-brain barrier. microRNAs are associated with normal neuronal functioning, as well as brain aging and ND development. microRNA-based assays are already used by oncologists as part of “rule-in/rule-out” diagnostic panels. The data generated by our company demonstrate the potential use of circulating brain-enriched and inflammation-associated microRNAs as biomarkers for detecting and assessing the course of AD at early, including preclinical, and later stages. We discovered miR-132 and miR-134 biomarker families capable of differentiating mild cognitive impairment from controls with over 0.90 accuracy and of predicting cognitive decline 6 years prior to clinical manifestation. Further, using the same targeted approach, we showed that microRNA classifiers can effectively differentiate between AD, FTD, PD, and ALS. 

The main objective of this study is to assess associations between promising microRNA biomarker candidates and AD risk factors as well as known biomarkers, such as amyloid and APOE, in a well-characterized cross-sectional cohort. This study will help us address this important question and better understand how brain-enriched microRNAs detectable in plasma could be used in combination with other biomarkers in screening and diagnostic settings.