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Plasma microRNA biomarkers for detection of mild cognitive impairment.

ABSTRACT: Early stages of many neurodegenerative diseases, such as Alzheimer's disease, vascular and frontotemporal dementia, and Parkinson's disease, are frequently associated with Mild Cognitive Impairment (MCI). A minimally invasive screening test for early detection of MCI may be used to select optimal patient groups in clinical trials, to monitor disease progression and response to treatment, and to better plan patient clinical care. Here, we examined the feasibility of using pairs of brain-enriched plasma microRNA (miRNA), at least one of which is enriched in synapses and neurites, as biomarkers that could differentiate patients with MCI from age-matched controls. The identified biomarker pairs fall into two sets: the "miR-132 family" (miR-128/miR-491-5p, miR-132/miR-491-5p and mir-874/miR-491-5p) and the "miR-134 family" (miR-134/miR-370, miR-323-3p/miR-370 and miR-382/miR-370). The area under the Receiver-Operating Characteristic curve for the differentiation of MCI from controls using these biomarker pairs is 0.91-0.95, with sensitivity and specificity at 79%-100% (miR-132 family) and 79%-95% (miR-134 family), and p?0.001. In a separate longitudinal study, the identified miRNA biomarker pairs successfully detected MCI in majority of patients at asymptomatic stage 1-5 years prior to clinical diagnosis. The reported biomarker pairs also appear useful for detecting age-related brain changes. Further testing in a larger study is necessary for validation of these results.

SUBMITTER: Sheinerman KS

PROVIDER: S-EPMC3492224 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Plasma microRNA biomarkers for detection of mild cognitive impairment.

Sheinerman Kira S KS Tsivinsky Vladimir G VG Crawford Fiona F Mullan Michael J MJ Abdullah Laila L Umansky Samuil R SR

Aging 20120901 9

Early stages of many neurodegenerative diseases, such as Alzheimer's disease, vascular and frontotemporal dementia, and Parkinson's disease, are frequently associated with Mild Cognitive Impairment (MCI). A minimally invasive screening test for early detection of MCI may be used to select optimal patient groups in clinical trials, to monitor disease progression and response to treatment, and to better plan patient clinical care. Here, we examined the feasibility of using pairs of brain-enriched ...[more]

PMID: 23001356

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Project description:Plasma-based biomarkers present a promising approach in the research and clinical practice of Alzheimer's disease as they are inexpensive, accessible and minimally invasive. In particular, prognostic biomarkers of cognitive decline may aid in planning and management of clinical care. Although recent studies have demonstrated the prognostic utility of plasma biomarkers of Alzheimer pathology or neurodegeneration, such as pTau-181 and NF-L, whether other plasma biomarkers can further improve prediction of cognitive decline is undetermined. We conducted an observational cohort study to determine the prognostic utility of plasma biomarkers in predicting progression to dementia for individuals presenting with mild cognitive impairment due to probable Alzheimer's disease. We used the Olink™ Proximity Extension Assay technology to measure the level of 460 circulating proteins in banked plasma samples of all participants. We used a discovery data set comprised 60 individuals with mild cognitive impairment (30 progressors and 30 stable) and a validation data set consisting of 21 stable and 21 progressors. We developed a machine learning model to distinguish progressors from stable and used 44 proteins with significantly different plasma levels in progressors versus stable along with age, sex, education and baseline cognition as candidate features. A model with age, education, APOE genotype, baseline cognition, plasma pTau-181 and 12 plasma Olink protein biomarker levels was able to distinguish progressors from stable with 86.7% accuracy (mean area under the curve = 0.88). In the validation data set, the model accuracy was 78.6%. The Olink proteins selected by the model included those associated with vascular injury and neuroinflammation (e.g. IL-8, IL-17A, TIMP-4, MMP7). In addition, to compare these prognostic biomarkers to those that are altered in Alzheimer's disease or other types of dementia relative to controls, we analyzed samples from 20 individuals with Alzheimer, 30 with non-Alzheimer dementias and 34 with normal cognition. The proteins NF-L and PTP-1B were significantly higher in both Alzheimer and non-Alzheimer dementias compared with cognitively normal individuals. Interestingly, the prognostic markers of decline at the mild cognitive impairment stage did not overlap with those that differed between dementia and control cases. In summary, our findings suggest that plasma biomarkers of inflammation and vascular injury are associated with cognitive decline. Developing a plasma biomarker profile could aid in prognostic deliberations and identify individuals at higher risk of dementia in clinical practice.

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Plasma microRNA biomarkers for detection of mild cognitive impairment.

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Plasma microRNA biomarkers for detection of mild cognitive impairment.

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