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

Authors: Islam M, Kauran, L, Berulava T, Heilbronner U, Budde M, Centeno T, Elerdashvili V, Zafieriou M, Benito E, Sertel S, Goldberg M, Senner F, Kalman J, Burkhardt S, Oepen A, Sakib M, Kerimolgu C, Wirths O, Bickeböller H, Bartels C, Brosseron F, Buerger K, Cosma N, Fliessbach K, Heneka M, Janowitz D, Kilimann I, Kleinedam L, Laske C, Metzger C, Munk M, Perneczky R, Peters O, Priller J, Rauchmann B, Roy N, Schneider A, Spottke A, Spruth E, Teipel S, Tscheuschler M, Wagner M, Wiltfang J, Düzel E, Jessen F, Rizzoli S, Zimmermann W, Schulze T, Falkai P, Sananbenesi F and Fischer A.

EMBO Molecular Medicine, 2021.

 

Scientists using human subjects and animal models uncover microRNA signature that may lead to new ways to identify and treat cognitive disease 

Identifying biomarkers for Alzheimer’s disease and other age-related neurodegenerative disorders has the potential to allow for earlier diagnoses and new therapeutic targets, but research into this area has been challenging. However, a study of human subjects and animal models reveals a circulating 3-microRNA signature associated with cognitive decline—a finding that could be used in the future to detect individuals who are at risk for dementia with a simple blood test and enable further diagnostic procedures and early intervention. Significantly, the research also demonstrated that mice treated with an anti-microRNA-mix exhibited improved cognitive abilities, results that could lead to the development of biomarker-guided therapies for dementia.

To identify the 3-microRNA signature, researchers analyzed humans with and without cognitive decline, as well as animal and cellular disease models, and found the biomarker is increased not only in the blood, but also in the brains of mice with cognitive impairment and in the cerebrospinal fluid of people diagnosed with mild cognitive impairment. Along with other testing, scientists used Axion’s Maestro APEX platform to assess spontaneous in vitro activity of mouse hippocampal neurons treated with the 3-microRNA-mix and found that the cells demonstrated impaired neural plasticity, with the weighted mean firing rate, number of bursts, and network bursts all significantly reduced. Taken together with other results, the authors suggest that the identification this 3-microRNA signature associated with cognitive decline could be used in the future to screen older adults for dementia and provide targets for the development of novel RNA-based therapeutics.