Alzheimer’s disease and Dementia with Lewy bodies (DLB) are two very heterogeneous and complex neurodegenerative dementias. Both disorders have a similar age of onset and feature cognitive impairment such as short-term memory loss. DLB is also accompanied with hallucinations and, in many cases, motor dysfunctions as well as parkinsonism. Their neuropathological and clinical parameters overlap and therefore leads to misdiagnosis, resulting in incorrect treatment and clinical management of patients with DLB. Hence, it is crucial to find a more effective and precise non-invasive diagnostic tool, in order to better differentiate between these two diseases.
illustration: MicroRNAs (green structures) are known to inhibit (red « T » line) the expression of specific proteins (shown inside the neurons). Their expression were monitored in isolated Extracellular Vesicles (EVs) from either healthy people or patient with dementia (Alzheimer and with Lewy bodies). Those EVs, isolated from blood, are thought to originate from brain cells. The expression of two microRNA (451a; 21-5p) was down-regulated only in patient with Alzheimer. This new method allows a better distinction of the two types of dementia, which was not possible so far.
Like most of cells in human body, neurons and other brain cells are able to secrete extracellular vesicles (EVs) in the central nervous system. EVs that are surrounded by lipid bilayer membranes can be formed either in the cell cytoplasm (and later secreted -exosomes-) or by cell membrane protrusions-microvesicles-. They contain proteins, lipids, and nucleic acids (different types of RNA, in particular microRNAs). MicroRNAs are small non-coding RNAs that regulate mRNA (messenger RNA) expression, resulting in gene silencing, preventing the production of specific proteins. The EVs secreted by neurons and other brain cells are released into the cerebrospinal fluid by crossing the blood-brain barrier. Studying these vesicles could help to elucidate the neurodegenerative processes occurring in the brain. However, isolation of these vesicles directly from the cerebrospinal fluid is an invasive, traumatic and painful process for aged patients. For this reason, it has been proposed to study EVs coming from the brain, which after crossing the blood-brain barrier, could be detected in the blood.
In this context, Francesc E. Borràs’ and Katrin Beyer’s groups (Instituto de Investigación Germans Trias i Pujol (IGTP), Badalona, Spain) hypothesized that EVs from patients’ plasma may reflect molecular changes occurring in patients’ brains. Interestingly, Dr Ana Gámez-Valero and co. discovered that two microRNAs contained in plasma-EVs, hsa-miR-451a (451a) and hsa-miR-21-5p (21-5p), were downregulated in Alzheimer’s disease compared to healthy individuals and patients with DLB.
In conclusion, via the detection of two microRNAs (451a; 21-5p), scientists succeeded in developing a new molecular tool that can be used to differentiate Alzheimer’s disease and Dementia with Lewy bodies in a non-invasive, highly specific and sensitive manner.
Illustration: Line Hurtado and Dr. Sarah Hurtado-Bagès (sci.sters.editions)
Graphic design: Line Hurtado (sci.sters.editions)
Text: written by Dr. Ana Gámez-Valero (EN, ES), corrected and translated by Dr. Sarah Hurtado-Bagès (EN, FR), Richard Norris (EN) and Line Hurtado (FR)
Financial support of the scientific research shown: supported by Spain’s Ministry of Health, project PI15/00216, integrated in the National R + D +I and funded by the ISCIII and the European Regional Development Fund. It was also supported by the MaratóTV3 grant 201405/10