Periaqueductal gray matter echogenicity as a marker of migraine chronification : a case control study

Migraine is one of the most prevalent and disabling medical diseases in the world. The periaqueductal gray matter and the red nucleus play an important role in its pathogenesis. Our aim was to evaluate the echogenicity of the periaqueductal gray matter and the red nucleus in patients with migraine, by means of transcranial ultrasound. In this cross-sectional study, a group of patients with migraine (according to the International Classification of Headache Disorders) and a group of control subjects with comparable age-and-sex distribution were prospectively included. We evaluated the area and echogenicity of the periaqueductal gray matter and the red nucleus by means of transcranial ultrasound, both bedside and posteriorly analyzed with the medical image viewer Horos. We included 115 subjects: 65 patients with migraine (39 of them with chronic migraine and 26 with episodic migraine), and 50 controls. Median disease duration in patients with chronic migraine was 29 (IQR: 19; 40) years, with a median of 18 (IQR: 14; 27) days of migraine per month. The area of the periaqueductal gray matter was larger in patients with chronic migraine compared to episodic migraine and controls (0.15[95%CI 0.12;0.22]cm 2 ; 0.11[95%CI 0.10;0.14]cm 2 and 0.12[95%CI 0.09;0.15]cm 2, respectively; p = 0.043). Chronic migraine patients showed an intensity of the periaqueductal gray matter echogenicity lower than controls (90.57[95%CI 70.87;117.26] vs 109.56[95%CI 83.30;122.64]; p = 0.035). The coefficient of variation of periaqueductal gray matter echogenicity was the highest in chronic migraine patients (p = 0.009). No differences were observed regarding the area or intensity of red nucleus echogenicity among groups. Patients with chronic migraine showed a larger area of echogenicity of periaqueductal gray matter, a lower intensity of its echogenicity and a higher heterogenicity within this brainstem structure compared to patients with episodic migraine and controls. The echogenicity of the periaqueductal gray matter should be further investigated as a biomarker of migraine chronification. The online version contains supplementary material available at 10.1186/s10194-023-01576-3

Exploratory study on microRNA profiles from plasma-derived extracellular vesicles in Alzheimer's disease and dementia with Lewy bodies

Altres ajuts: This work was also supported by the MaratóTV3 grant 201405/10.Because of the increasing life expectancy in our society, aging-related neurodegenerative disorders are one of the main issues in global health. Most of these diseases are characterized by the deposition of misfolded proteins and a progressive cognitive decline. Among these diseases, Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the most common types of degenerative dementia. Although both show specific features, an important neuropathological and clinical overlap between them hampers their correct diagnosis. In this work, we identified molecular biomarkers aiming to improve the misdiagnosis between both diseases. Plasma extracellular vesicles (EVs) -from DLB, AD and healthy controls- were isolated using size-exclusion chromatography (SEC) and characterized by flow cytometry, Nanoparticle Tracking Analysis (NTA) and cryo-electron microscopy. Next Generation Sequencing (NGS) and related bibliographic search was performed and a selected group of EV-associated microRNAs (miRNAs) was analysed by qPCR. Results uncovered two miRNAs (hsa-miR-451a and hsa-miR-21-5p) significantly down-regulated in AD samples respect to DLB patients, and a set of four miRNAs (hsa-miR-23a-3p, hsa-miR-126-3p, hsa-let-7i-5p, and hsa-miR-151a-3p) significantly decreased in AD respect to controls. The two miRNAs showing decreased expression in AD in comparison to DLB provided area under the curve (AUC) values of 0.9 in ROC curve analysis, thus suggesting their possible use as biomarkers to discriminate between both diseases. Target gene analysis of these miRNAs using prediction online tools showed accumulation of phosphorylation enzymes, presence of proteasome-related proteins and genes involved in cell death among others. Our data suggest that plasma-EV associated miRNAs may reflect a differential profile for a given dementia-related disorder which, once validated in larger cohorts of patients, could help to improve the differential diagnosis of DLB versus AD. The online version of this article (10.1186/s40035-019-0169-5) contains supplementary material, which is available to authorized users

Expression Levels of an Alpha-Synuclein Transcript in Blood May Distinguish between Early Dementia with Lewy Bodies and Parkinson's Disease

Lewy body diseases (LBD) including dementia with Lewy bodies (DLB) and Parkinson disease (PD) are characterized by alpha-synuclein pathology. DLB is difficult to diagnose and peripheral biomarkers are urgently needed. Therefore, we analyzed the expression of five alpha-synuclein gene (SNCA) transcripts, SNCAtv1, SNCAtv2, SNCAtv3, SNCA126, and SNCA112, in 45 LBD and control temporal cortex samples and in the blood of 72 DLB, 59 PD, and 54 control subjects. The results revealed overexpression of SNCAtv1 and SNCA112 in DLB, and SNCAtv2 in PD temporal cortices. In DLB blood, diminution of all SNCA transcripts was observed. SNCAtv1 and SNCAtv2 were diminished in PD with disease onset before 70 years. SNCAtv3, driven by its own promoter, showed opposite expression in early DLB and PD, suggesting that its amount may be an early, DLB specific biomarker. Correlation between blood transcript levels and disease duration was positive in DLB and negative in PD, possibly reflecting differences in brain alpha-synuclein aggregation rates associated with differences in disease courses. In conclusion, SNCA transcripts showed a disease-specific increase in the brain and were diminished in blood of LBD patients. SNCAtv3 expression was decreased in early DLB and increased in early PD and could be a biomarker for early DLB diagnosis

Platelet miRNA Biosignature Discriminates between Dementia with Lewy Bodies and Alzheimer’s Disease

Dementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia, after Alzheimer's disease (AD), and presents pathological and clinical overlap with both AD and Parkinson's disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets, previously related to neurodegeneration, contain microRNAs (miRNAs) whose analysis may provide disease biomarkers. Here, we profiled the whole platelet miRNA transcriptome from DLB patients and healthy controls. Differentially expressed miRNAs were further validated in three consecutive studies from 2017 to 2019 enrolling 162 individuals, including DLB, AD, and PD patients, and healthy controls. Results comprised a seven-miRNA biosignature, showing the highest diagnostic potential for the differentiation between DLB and AD. Additionally, compared to controls, two miRNAs were down-regulated in DLB, four miRNAs were up-regulated in AD, and two miRNAs were down-regulated in PD. Predictive target analysis identified three disease-specific clusters of pathways as a result of platelet-miRNA deregulation. Our cross-sectional study assesses the identification of a novel, highly specific and sensitive platelet-associated miRNA-based biosignature, which distinguishes DLB from AD

Glucocerebrosidase Mrna Is Diminished In Brain Of Lewy Body Diseases And Changes With Disease Progression In Blood

Parkinson disease (PD) and dementia with Lewy bodies (DLB) are Lewy body diseases characterized by abnormal alpha-synuclein deposits and overlapping pathological features in the brain. Several studies have shown that glucocerebrosidase (GBA) deficiency is involved in the development of LB diseases. Here, we aimed to find out if this deficiency starts at the transcriptional level, also involves alternative splicing, and if GBA expression changes in brain are also detectable in blood of patients with LB diseases. The expression of three GBA transcript variants (GBAtv1, GBAtv2 and GBAtv5) was analyzed in samples from 20 DLB, 25 PD and 17 control brains and in blood of 20 DLB, 26 PD patients and 17 unaffected individuals. Relative mRNA expression was determined by real-time PCR. Expression changes were evaluated by the Delta Delta Ct method. In brain, specific expression profiles were identified in the temporal cortex of DLB and in the caudate nucleus of PD. In blood, significant GBA mRNA diminution was found in both DLB and PD patients. Early PD and early-onset DLB patients showed lowest GBA levels which were normal in PD patients with advanced disease and DLB patients who developed disease after 70 years of age. In conclusion, disease group specific GBA expression profiles were found in mostly affected areas of LBD. In blood, GBA expression was diminished in LB diseases, especially in patients with early onset DLB and in patients with early PD. Age of disease onset exerts an opposite effect on GBA expression in DLB and PD

New spinocerebellar ataxia subtype caused by SAMD9L mutation triggering mitochondrial dysregulation (SCA49)

Spinocerebellar ataxias consist of a highly heterogeneous group of inherited movement disorders clinically characterized by progressive cerebellar ataxia variably associated with additional distinctive clinical signs. The genetic heterogeneity is evidenced by the myriad of associated genes and underlying genetic defects identified. In this study, we describe a new spinocerebellar ataxia subtype in nine members of a Spanish five-generation family from Menorca with affected individuals variably presenting with ataxia, nystagmus, dysarthria, polyneuropathy, pyramidal signs, cerebellar atrophy and distinctive cerebral demyelination. Affected individuals presented with horizontal and vertical gaze-evoked nystagmus and hyperreflexia as initial clinical signs, and a variable age of onset ranging from 12 to 60 years. Neurophysiological studies showed moderate axonal sensory polyneuropathy with altered sympathetic skin response predominantly in the lower limbs. We identified the c.1877C > T (p.Ser626Leu) pathogenic variant within the SAMD9L gene as the disease causative genetic defect with a significant log-odds score (Z(max) = 3.43; theta = 0.00; P < 3.53 x 10(-5)). We demonstrate the mitochondrial location of human SAMD9L protein, and its decreased levels in patients' fibroblasts in addition to mitochondrial perturbations. Furthermore, mutant SAMD9L in zebrafish impaired mobility and vestibular/sensory functions. This study describes a novel spinocerebellar ataxia subtype caused by SAMD9L mutation, SCA49, which triggers mitochondrial alterations pointing to a role of SAMD9L in neurological motor and sensory functions. Corral-Juan et al. describe a novel dominantly inherited spinocerebellar ataxia subtype, SCA49, caused by SAMD9L mutation characterized by polyneuropathy, distinctive cerebral demyelination with gaze-evoked nystagmus and hyperreflexia as initial clinical signs. The study demonstrates the mitochondrial location of human SAMD9L protein triggering mitochondrial and lysosomal alterations

Sporadic Creutzfeldt-Jakob disease VM1: phenotypic and molecular characterization of a novel subtype of human prion disease

The methionine (M)-valine (V) polymorphic codon 129 of the prion protein gene (PRNP) plays a central role in both susceptibility and phenotypic expression of sporadic Creutzfeldt-Jakob diseases (sCJD). Experimental transmissions of sCJD in humanized transgenic mice led to the isolation of five prion strains, named M1, M2C, M2T, V2, and V1, based on two major conformations of the pathological prion protein (PrPSc, type 1 and type 2), and the codon 129 genotype determining susceptibility and propagation efficiency. While the most frequent sCJD strains have been described in codon 129 homozygosis (MM1, MM2C, VV2) and heterozygosis (MV1, MV2K, and MV2C), the V1 strain has only been found in patients carrying VV. We identified six sCJD cases, 4 in Catalonia and 2 in Italy, carrying MV at PRNP codon 129 in combination with PrPSc type 1 and a new clinical and neuropathological profile reminiscent of the VV1 sCJD subtype rather than typical MM1/MV1. All patients had a relatively long duration (mean of 20.5 vs. 3.5 months of MM1/MV1 patients) and lacked electroencephalographic periodic sharp-wave complexes at diagnosis. Distinctive histopathological features included the spongiform change with vacuoles of larger size than those seen in sCJD MM1/MV1, the lesion profile with prominent cortical and striatal involvement, and the pattern of PrPSc deposition characterized by a dissociation between florid spongiform change and mild synaptic deposits associated with coarse, patch-like deposits in the cerebellar molecular layer. Western blot analysis of brain homogenates revealed a PrPSc type 1 profile with physicochemical properties reminiscent of the type 1 protein linked to the VV1 sCJD subtype. In summary, we have identified a new subtype of sCJD with distinctive clinicopathological features significantly overlapping with those of the VV1 subtype, possibly representing the missing evidence of V1 sCJD strain propagation in the 129MV host genotype

Multicentre, randomised, single-blind, parallel group trial to compare the effectiveness of a Holter for Parkinson's symptoms against other clinical monitoring methods: study protocol

Introduction In recent years, multiple studies have aimed to develop and validate portable technological devices capable of monitoring the motor complications of Parkinson's disease patients (Parkinson's Holter). The effectiveness of these monitoring devices for improving clinical control is not known. Methods and analysis This is a single-blind, cluster-randomised controlled clinical trial. Neurologists from Spanish health centres will be randomly assigned to one of three study arms (1:1:1): (a) therapeutic adjustment using information from a Parkinson?s Holter that will be worn by their patients for 7 days, (b) therapeutic adjustment using information from a diary of motor fluctuations that will be completed by their patients for 7 days and (c) therapeutic adjustment using clinical information collected during consultation. It is expected that 162 consecutive patients will be included over a period of 6 months. The primary outcome is the efficiency of the Parkinson?s Holter compared with traditional clinical practice in terms of Off time reduction with respect to the baseline (recorded through a diary of motor fluctuations, which will be completed by all patients). As secondary outcomes, changes in variables related to other motor complications (dyskinesia and freezing of gait), quality of life, autonomy in activities of daily living, adherence to the monitoring system and number of doctor?patient contacts will be analysed. The noninferiority of the Parkinson's Holter against the diary of motor fluctuations in terms of Off time reduction will be studied as the exploratory objective. Ethics and dissemination approval for this study has been obtained from the Hospital Universitari de Bellvitge Ethics Committee. The results of this study will inform the practical utility of the objective information provided by a Parkinson's Holter and, therefore, the convenience of adopting this technology in clinical practice and in future clinical trials. We expect public dissemination of the results in 2022.Funding This work is supported by AbbVie S.L.U, the Instituto de Salud Carlos III [DTS17/00195] and the European Fund for Regional Development, 'A way to make Europe'

Aplicaciones de la ultrasonografía transcraneal en los trastornos del movimiento

El diagnòstic de la malaltia de Parkinson (MP) i de la major part de trastorns del moviment es basa fonamentalment en criteris clínics. No obstant això, existeix un important solapament fenotípic i anatomopatològic que pot dificultar en gran manera el diagnòstic diferencial, especialment en fases inicials de la malaltia. La ultrasonografía transcranial ha sorgit com una tècnica no invasiva, de ràpida execució i baix cost econòmic, de gran utilitat com a eina complementària en el diagnòstic diferencial dels trastorns del moviment. La hipòtesi plantejada en aquesta tesi doctoral és que aquesta tècnica pot ser útil en la pràctica clínica diària d'una unitat de trastorns del moviment (UTM) per a l'estudi de la MP, el seu diagnòstic diferencial amb altres quadres que cursin amb tremolor i/o parkinsonisme i l'estudi d'altres trastorns del moviment hipercinètics com la síndrome de Gilles de la Tourette (SGT). Per a demostrar aquesta hipòtesi s'han dut a terme 4 treballs amb diferents grups mostrals procedents d'una consulta d'UTM i controls sans. Es van analitzar variables sonogràfiques com l'àrea de substància nigra (SN) hiperecogènica, tamany del tercer ventricle i de la banya frontal del ventricle lateral, ecogenicitat dels nuclis del rafe i del nucli lenticular. En el primer treball es va estudiar un grup control sa per a establir els punts de tall patològics per a les variables sonogràfiques quantitatives i es va analitzar la utilitat de les troballes sonogràfiques per al diagnòstic diferencial de la MP enfront d'altres patologies que cursen amb tremolor i/o parkinsonisme. En el segon treball es va intentar identificar si alguna variable sonogràfica servia com a marcador d'un fenotip clínic concret en la MP (major severitat, predomini tremòric o rígid-acinètic, presència de símptomes no motors). En el tercer treball es va comprovar la utilitat de la tècnica, comparada amb tècniques de neuroimatge convencional, per a la comprovació postoperatòria precoç dels elèctrodes d'estimulació cerebral profunda (ECP) en el nucli subtalàmic (NST) en la MP. En el quart treball es van estudiar les troballes sonogràfiques en pacients amb SGT. S'ha demostrat que l'estudi sonogràfic de l'àrea de SN hiperecogènica és útil per al diagnòstic diferencial entre MP, tremolor i altres parkinsonismes (atípics i secundaris), l'estudi del tamany ventricular i l'ecogenicitat del lenticular són útils per a identificar parkinsonismes atípics. Una SN hiperecogènica, una hiperecogenicitat lenticular i un major tamany del ventricle lateral correlacionen amb majors puntuacions en l'escala Hoehn i Yahr; aquest últim s'associa també a una major afectació axial i de la marxa. Pacients amb complicacions motores mostren majors àrees de SN, la grandària del tercer ventricle va ser major si hi havia al·lucinacions visuals i el ventricle lateral va ser major en pacients amb hiposmia, el rafe va ser més sovint hipoecogènic en presència de depressió. La sonografía transcranial és útil per a la comprovació postoperatòria precoç dels elèctrodes d'ECP en el NST. En el SGT s'ha detectat un augment significatiu de la hiperecogenicitat lenticular en comparació amb controls sans. Per tant, els resultats d'aquesta recerca donen suport a l'ús de la ultrasonografía transcranial per a l'estudi dels trastorns del moviment en la pràctica clínica habitual d'una UTM. Són necessàries noves línies de recerca destinades a corroborar aquests resultats i ampliar l'estudi a altres trastorns del moviment poc explorats fins ara.El diagnóstico de la enfermedad de Parkinson (EP) y de la mayor parte de trastornos del movimiento se basa fundamentalmente en criterios clínicos. Sin embargo, existe un importante solapamiento fenotípico y anatomopatológico que puede dificultar en gran medida el diagnóstico diferencial, especialmente en fases iniciales de la enfermedad. La ultrasonografía transcraneal ha surgido como una técnica no invasiva, de rápida ejecución y bajo coste económico, de gran utilidad como herramienta complementaria en el diagnóstico diferencial de los trastornos del movimiento. La hipótesis planteada en esta tesis doctoral es que esta técnica puede ser útil en la práctica clínica diaria de una unidad de trastornos del movimiento (UTM) para el estudio de la EP, su diagnóstico diferencial con otros cuadros que cursen con temblor y/o parkinsonismo y el estudio de otros trastornos del movimiento hipercinéticos como el síndrome de Gilles de la Tourette (SGT). Para demostrar esta hipótesis se han llevado a cabo 4 trabajos con diferentes grupos muestrales procedentes de una consulta de UTM y controles sanos. Se analizaron variables sonográficas como el área de sustancia negra (SN) hiperecogénica, tamaño del tercer ventrículo y del asta frontal del ventrículo lateral, ecogenicidad de los núcleos del rafe y del núcleo lenticular. En el primer trabajo se estudió un grupo control sano para establecer los puntos de corte patológicos para las variables sonográficas cuantitativas y se analizó la utilidad de los hallazgos sonográficos para el diagnóstico diferencial de la EP frente a otras patologías que cursan con temblor y/o parkinsonismo. En el segundo trabajo se intentó identificar si alguna variable sonográfica servía como marcador de un fenotipo clínico concreto en la EP (mayor severidad, predominio tremórico o rígido-acinético, presencia de síntomas no motores). En el tercer trabajo se comprobó la utilidad de la técnica, comparada con técnicas de neuroimagen convencional, para la comprobación postoperatoria precoz de los electrodoimulación cerebral profunda (ECP) en el núcleo subtalámico en la EP. En el cuarto trabajo se estudiaron los hallazgos sonográficos en pacientes con SGT. Se ha demostrado que el estudio sonográfico del área de SN hiperecogénica es útil para el diagnóstico diferencial entre EP, temblor y otros parkinsonismos (atípicos y secundarios), el estudio del tamaño ventricular y la ecogenicidad del lenticular son útiles para identificar parkinsonismos atípicos. Una SN hiperecogénica, una hiperecogenicidad lenticular y un mayor tamaño del ventrículo lateral correlacionan con mayores puntuaciones en la escala Hoehn y Yahr; éste último se asocia también a una mayor afectación axial y de la marcha. Pacientes con complicaciones motoras muestran mayores áreas de SN, el tamaño del tercer ventrículo fue mayor si había alucinaciones visuales y el del ventrículo lateral fue mayor en pacientes con hiposmia, el rafe fue más frecuentemente hipoecogénico en presencia de depresión. La sonografía transcraneal es útil para la comprobación postoperatoria precoz de los electrodos de ECP en el NST. En el SGT se ha detectado un aumento significativo de la hiperecogenicidad lenticular en comparación con controles sanos. Por tanto, los resultados de esta investigación apoyan el uso de la ultrasonografía transcraneal para el estudio de los trastornos del movimiento en la práctica clínica habitual de una unidad de trastornos del movimiento. Son necesarias nuevas líneas de investigación destinadas a corroborar estos resultados y ampliar el estudio a otros trastornos del movimiento poco explorados hasta la fecha.The diagnosis of Parkinson's disease (PD) and most movement disorders is based mainly on clinical criteria. However, there is a significant phenotypic and anatomopathological overlap that can make differential diagnosis very difficult, especially in the early stages of the disease. Transcranial ultrasonography has emerged as a non-invasive technique, of rapid execution and low economic cost, very useful as a complementary tool in the differential diagnosis of movement disorders. The hypothesis put forward in this doctoral thesis is that this technique may be useful in the daily clinical practice of a movement disorders unit (MDU) for the study of PD, its differential diagnosis with other conditions with tremor and/or parkinsonism and the study of other hyperkinetic movement disorders such as Gilles de la Tourette syndrome (GTS). In order to demonstrate this hypothesis, four studies have been carried out with different sample groups from a UTM outpatient consultation, and healthy controls. Sonographic variables such as the area of hyperechogenic substantia nigra (SN), size of the third ventricle and the frontal shaft of the lateral ventricle, ecogenicity of raphe nuclei and lenticular nuclei were analysed. In the first work a healthy control group was studied to establish the pathological cut-off points for the quantitative sonographic variables and the usefulness of the sonographic findings for the differential diagnosis of PD against other pathologies with tremor and/or parkinsonism was analysed. In the second work, an attempt was made to identify whether any sonographic variable served as a marker for a particular clinical phenotype in PD (greater severity, predominance of tremor or rigid-akinetic, presence of non-motor symptoms). In the third study, the usefulness of the technique, compared to conventional neuroimaging techniques, for early postoperative testing of deep brain stimulation (DBS) electrodes in the subthalamic nucleus (STN) in PD was tested. In the fourth study, sonographic findings were studied in patients with GTS. Sonographic study of the hyperechogenic SN area has been shown to be useful for the differential diagnosis between PD, tremor and other parkinsonisms (atypical and secondary), the study of ventricular size and lenticular ecogenicity are useful to identify atypical parkinsonisms. Hyperechogenic SN, lenticular hyperechogenicity and larger lateral ventricle size correlate with higher scores on the Hoehn and Yahr scale; the latter is also associated with greater axial and gait involvement. Patients with motor complications show greater areas of SN, the size of the third ventricle was larger if there were visual hallucinations and the lateral ventricle was larger in patients with hyposmia, the lenticular was more frequently hyperechogenic in the presence of depression. Transcranial sonography is useful for early postoperative testing of DBS electrodes in the STN. A significant increase in lenticular hyperechogenicity has been detected in the GTS compared to healthy controls. Therefore, the results of this research support the use of transcranial ultrasonography for the study of movement disorders in the routine clinical practice of a movement disorders unit. New lines of research are needed to corroborate these results and extend the study to other movement disorders that have been little explored to date.Universitat Autònoma de Barcelona. Programa de Doctorat en Medicin

Exploratory study on microRNA profiles from plasma-derived extracellular vesicles in Alzheimer's disease and dementia with Lewy bodies

Altres ajuts: This work was also supported by the MaratóTV3 grant 201405/10.Because of the increasing life expectancy in our society, aging-related neurodegenerative disorders are one of the main issues in global health. Most of these diseases are characterized by the deposition of misfolded proteins and a progressive cognitive decline. Among these diseases, Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the most common types of degenerative dementia. Although both show specific features, an important neuropathological and clinical overlap between them hampers their correct diagnosis. In this work, we identified molecular biomarkers aiming to improve the misdiagnosis between both diseases. Plasma extracellular vesicles (EVs) -from DLB, AD and healthy controls- were isolated using size-exclusion chromatography (SEC) and characterized by flow cytometry, Nanoparticle Tracking Analysis (NTA) and cryo-electron microscopy. Next Generation Sequencing (NGS) and related bibliographic search was performed and a selected group of EV-associated microRNAs (miRNAs) was analysed by qPCR. Results uncovered two miRNAs (hsa-miR-451a and hsa-miR-21-5p) significantly down-regulated in AD samples respect to DLB patients, and a set of four miRNAs (hsa-miR-23a-3p, hsa-miR-126-3p, hsa-let-7i-5p, and hsa-miR-151a-3p) significantly decreased in AD respect to controls. The two miRNAs showing decreased expression in AD in comparison to DLB provided area under the curve (AUC) values of 0.9 in ROC curve analysis, thus suggesting their possible use as biomarkers to discriminate between both diseases. Target gene analysis of these miRNAs using prediction online tools showed accumulation of phosphorylation enzymes, presence of proteasome-related proteins and genes involved in cell death among others. Our data suggest that plasma-EV associated miRNAs may reflect a differential profile for a given dementia-related disorder which, once validated in larger cohorts of patients, could help to improve the differential diagnosis of DLB versus AD. The online version of this article (10.1186/s40035-019-0169-5) contains supplementary material, which is available to authorized users