Novel Blood Test Could Reveal Alzheimer’s Disease Biology and Risk for Progression

The inability to diagnose Alzheimer’s disease, the most prevalent form of dementia in the elderly, at an early stage of molecular pathology is considered a key reason why treatments fail in clinical trials. Previous efforts to diagnose Alzheimer’s molecularly have focused on the central biomarkers of β-amyloid, Tau, and Neurodegeneration (A/T/N), which are measured through the analysis of proteins associated with neurodegeneration. A/T/N can be assessed in brain tissue, through in vivo brain imaging techniques, and by analyzing cerebrospinal fluid and plasma. Alzheimer’s disease is believed to be triggered by a combination of genetic and environmental risk factors. Blood-based biomarkers, such as plasma microRNAs (miRNAs)—molecules that regulate interactions between the genome and the environment and control the expression of genes governing brain functions that deteriorate in Alzheimer’s—could offer advantages in terms of cost-effectiveness, accessibility, and reduced invasiveness.

Two new papers by a research team, including investigators from Boston University (Boston, MA, USA), have demonstrated that evaluating microRNAs in blood can be used not only to diagnose mild cognitive impairment (MCI) but also, crucially, to predict the progression from MCI to dementia due to Alzheimer’s disease. Additionally, the researchers identified microRNA candidate molecular biomarkers associated with the current A/T/N Alzheimer’s biomarkers. In their study, the team analyzed miRNA expression in plasma samples from three groups of participants—those who were cognitively normal, those with mild cognitive impairment, and those with dementia due to Alzheimer’s disease. They discovered that, when combined with neuropsychological testing, plasma microRNAome evaluation could help predict which aging individuals concerned about cognitive decline are likely to develop Alzheimer’s.

Although novel therapies for Alzheimer’s disease are beginning to enter clinical care, the researchers emphasize that these treatments will only be effective if patients at risk are identified as early as possible. The researchers highlight the need for improved tools for early detection of Alzheimer’s, which are essential for developing prevention and treatment strategies for a disease that causes significant suffering and places a heavy burden on healthcare systems worldwide. These findings are published in Alzheimer’s & Dementia.

“Our papers are the result of a successful collaboration that tied the technology developed by professor Andre Fischer in Germany’s DZNE to reliably measure the levels of microRNA in human plasma, and the power of blood samples obtained from hundreds of ADNI participants participating in a simulated clinical trial taking place at about 60 medical centers across the US and Canada,” explained one of four senior authors Ivana Delalle, MD, PhD, professor of pathology & laboratory medicine at Boston University Chobanian & Avedisian School of Medicine. “Our discovery is important because, unlike the current A/T/N biomarkers, microRNAs may serve as blood molecular biomarkers years before Alzheimer’s disease manifests clinically, thus identifying the time window for effective prevention or early intervention to stop the progression of Alzheimer’s.”

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