A microRNA signature that correlates with cognition and is a target against cognitive decline

Abstract

While some individuals age without pathological memory impairments, others develop age‐associated cognitive diseases. Since changes in cognitive function develop slowly over time in these patients, they are often diagnosed at an advanced stage of molecular pathology, a time point when causative treatments fail. Thus, there is great need for the identification of inexpensive and minimal invasive approaches that could be used for screening with the aim to identify individuals at risk for cognitive decline that can then undergo further diagnostics and eventually stratified therapies. In this study, we use an integrative approach combining the analysis of human data and mechanistic studies in model systems to identify a circulating 3‐microRNA signature that reflects key processes linked to neural homeostasis and inform about cognitive status. We furthermore provide evidence that expression changes in this signature represent multiple mechanisms deregulated in the aging and diseased brain and are a suitable target for RNA therapeutics.

MicroRNA Networks in Cognition and Dementia

“…Several groups have started investigating the role of miRNAs in this neurodegenerative progression. A new study used both a mouse model of aging and memory decline and a cohort of patients with MCI to identify a miRNA signature in circulating miRNAs dysregulated with cognitive impairment [ 19 ]. The levels of three miRNAs were altered in both mouse and human blood samples, namely, miR-181a, miR-148a, and miR-146a.…”

microRNAs trip down memory lane

“… (A) In some older individuals, normal cognitive function is prone to deteriorate into mild cognitive impairment (known also as mild neurocognitive disorder), which is considered a prodromal state of dementia, including primarily Alzheimer’s disease. (B) In a new work by Islam et al (2021), authors study human blood samples and mouse models of aging and dementia. They demonstrate a reciprocal correlation between brain function and the levels of three endogenous microRNAs in the blood, namely, miR‐181a‐5p, miR‐146‐5p, and miR‐148a‐3p.…”

“…In this issue of EMBO Molecular Medicine , Islam et al (2021) propose an original approach for screening healthy individuals at risk of cognitive decline. The approach is based on blood drawing and hence is “minimally invasive” and features the quantification of microRNAs (miRNAs) in the blood.…”

“…Utilizing such a framework, Islam et al (2021) addressed an intriguing research mission: to identify miRNAs that are informative about the cognitive state in healthy humans. They performed their analysis by correlating miRNA signatures in blood to the score gained by cognitive assessment tests.…”

Can mild cognitive impairment and Alzheimer’s disease be diagnosed by monitoring a miRNA triad in the blood?

“…Specific biomarkers that could be used consistently to diagnose ACI, MCI, or AD are yet to be discovered. This commentary discusses the recent findings by Islam and colleagues that the cognitive status of individuals could be gleaned from studying changes in a microRNA (miRNA) triad in the circulating blood (Islam et al, 2021). miRNAs are ~22 nucleotides long, have a post-transcriptional/ translational regulatory target, and have diverse sequences.…”