Two recent studies conducted by a group of researchers reveal that assessing microRNAs present in blood can be an effective method for diagnosing mild cognitive impairment (MCI) and, importantly, for predicting the progression from MCI to Alzheimer’s disease dementia. Additionally, the team identified potential microRNA molecular biomarkers that correlate with existing Alzheimer’s biomarkers classified as Amyloid, Tau, and Neurodegeneration (A/T/N).
The inability to identify Alzheimer’s disease—the leading type of dementia in older adults—at an early stage of molecular pathology is a significant factor contributing to the failure of treatments in clinical trials. Earlier research aimed at molecularly diagnosing Alzheimer’s disease resulted in the identification of “A/T/N” key biomarkers based on the detection of proteins such as β-amyloid (“A”) and tau (“T”), along with neurodegeneration (“N”). These biomarkers can be measured through brain tissue analysis, in vivo imaging techniques, and evaluations of cerebrospinal fluid and plasma.
Alzheimer’s disease is believed to be caused by a mix of genetic and environmental risk factors. Blood-based biomarkers, like plasma microRNAs (miRNAs)—which help regulate the interaction between genes and the environment and control gene expression related to brain functions that decline in Alzheimer’s—may offer benefits like lower costs, easier access, and reduced invasiveness compared to other diagnostic methods.
A collaborative research team from Boston University, Indiana University School of Medicine, the Alzheimer’s Disease Neuroimaging Initiative (ADNI), and the German Center for Neurodegenerative Diseases (DZNE) in Goettingen, Germany, published findings in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. Their work shows that analyzing blood microRNAs can aid in diagnosing mild cognitive impairment (MCI) and predict the transition from MCI to Alzheimer’s dementia. They also identified microRNA biomarkers linked to the current A/T/N Alzheimer’s biomarkers.
“Our research stems from a productive collaboration that utilized technology developed by Professor Andre Fischer at Germany’s DZNE to accurately measure microRNA levels in human plasma, as well as blood samples from hundreds of ADNI participants in a simulated clinical trial across approximately 60 medical centers in the US and Canada. This discovery is significant because microRNAs might serve as blood molecular biomarkers long before clinical symptoms of Alzheimer’s emerge, allowing for timely prevention or early intervention to halt the advancement of the disease,” stated Ivana Delalle, MD, PhD, one of the four senior authors and a professor of pathology & laboratory medicine at Boston University Chobanian & Avedisian School of Medicine.
The other senior contributors include Andre Fischer, PhD, a DZNE speaker and professor of epigenetics of neurodegenerative diseases at the University Medical Center Goettingen in Germany; Kwangsik Nho, PhD, professor of radiology and imaging sciences at the IU School of Medicine; and Andrew J. Saykin, PsyD, Raymond C. Beeler Professor of Radiology and director of the Center for Neuroimaging at the IU School of Medicine, also associated with the Indiana Alzheimer’s Disease Research Center. The research was supported by funding from the National Institutes of Health’s National Institute on Aging multisite project RF1AG078299, “MicroRNAs as Diagnostic and Prognostic Biomarker of Alzheimer’s Disease.”
The researchers assessed miRNA expression in plasma samples from three groups of participants: those who are cognitively normal, those with mild cognitive impairment, and patients with dementia due to Alzheimer’s disease. They concluded that combining plasma microRNA assessments with neuropsychological evaluations can help predict which older individuals worried about cognitive decline may progress to develop Alzheimer’s.
“Our findings pave the way for a deeper understanding of the molecular mechanisms leading to symptoms like plaques, tangles, and brain atrophy, potentially uncovering new therapeutic targets,” said Saykin.
Despite the promising developments in novel Alzheimer’s therapies entering practical use, the researchers emphasize that these treatments will only be effective if at-risk patients are identified as early as possible.
“MicroRNAs make ideal biomarkers as they are highly stable and can regulate entire molecular pathways, thus maintaining cellular balance. A single microRNA can influence multiple proteins within the same pathway,” Fischer explained. “Therefore, analyzing just a few microRNAs can provide insights into intricate pathological changes that reflect various pathways such as neuroinflammation, metabolic shifts, or synapse dysfunction. We need biomarkers that allow for screening in point-of-care situations, and our studies represent a crucial step towards that goal.”
“We’ve established a foundation for further exploration into the role of microRNAs in the development of Alzheimer’s disease,” Nho noted. “We foresee that once specific miRNA patterns are verified, analyzing blood microRNAs will be simplified, facilitating the integration of blood miRNA evaluations into clinical settings.”
The researchers believe that enhanced tools for early Alzheimer’s detection are essential for crafting effective prevention and treatment strategies for a disease that inflicts considerable distress and strains healthcare systems globally.
