Comprehensive proteomic profiling of plasma-derived Extracellular Vesicles from dementia with Lewy Bodies patients

Altres ajuts: Grant 201405/10 from Fundació La Marató TV3Proteins and nucleic acids contained in extracellular vesicles (EVs) are considered a feasible source of putative biomarkers for physiological and pathological conditions. Within the nervous system, not only neurons but also other brain cells are able to produce EVs, which have been involved in their physiological processes and also in the development and course of several neurodegenerative diseases. Among these, dementia with Lewy bodies (DLB) is the second cause of dementia worldwide, though most cases are missed or misdiagnosed as Alzheimer's disease (AD) due to the important clinical and pathological overlap between both diseases. In an attempt to find reliable biomarkers for DLB diagnosis, our group characterized the proteome of plasma-derived EVs from DLB patients compared to aged-matched healthy controls (HCs) using two different proteomic LC-MS/MS approaches. Remarkably, we found that gelsolin and butyrylcholinesterase were differentially identified between DLB and HCs. Further validation of these results using conventional ELISA techniques, and including an additional group of AD patients, pointed to decreased levels of gelsolin in plasma-EVs from DLB compared to HCs and to AD samples. Thus, gelsolin may be considered a possible biomarker for the differentiation between DLB and AD

Assessment of microbial plankton diversity as an ecological indicator in the NW Mediterranean coast

High-throughput sequencing of microbial assemblages has been proposed as an alternative methodology to the traditional ones used in marine monitoring and environmental assessment. Here, we evaluated pico- and nanoplankton diversity as ecological indicators in NW Mediterranean coastal waters by comparing their diversity in samples subjected to varying degrees of continental pressures. Using metabarcoding of the 16S and 18S rRNA genes, we explored whether alphadiversity indices, abundance of Operational Taxonomic Units and taxonomic groups (and their ratios) provide information on the ecological quality of coastal waters. Our results revealed that only eukaryotic diversity metrics and a limited number of prokaryotic and eukaryotic taxa displayed potential in assessing continental influences in our surveyed area, resulting thus in a restrained potential of microbial plankton diversity as an ecological indicator. Therefore, incorporating microbial plankton diversity in environmental assessment could not always result in a significant improvement of current marine monitoring strategies.Preprint2,35

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

Locus coeruleus connectivity alterations in late-life major depressive disorder during a visual oddball task

The Locus Coeruleus (LC) is the major source of noradrenergic neurotransmission. Structural alterations in the LC have been observed in neurodegenerative disorders and at-risk individuals, although functional connectivity studies between the LC and other brain areas have not been yet performed in these populations. Patients with late-life major depressive disorder (MDD) are indeed at increased risk for neurodegenerative disorders, and here we investigated LC connectivity in late-life MDD in comparison to individuals with amnestic type mild cognitive impairment (aMCI) and healthy controls (HCs). We assessed 20 patients with late-life MDD, 16 patients with aMCI, and 26 HCs, who underwent a functional magnetic resonance scan while performing a visual oddball task. We assessed task-related modulations of LC connectivity (i.e., Psychophysiological Interactions, PPI) with other brain areas. A T1-weighted fast spin-echo sequence for LC localization was also obtained. Patients with late-life MDD showed lower global connectivity during target detection in a cluster encompassing the right caudal LC. Specifically, we observed lower LC connectivity with the left anterior cingulate cortex (ACC), the right fusiform gyrus, and different cerebellar clusters. Moreover, alterations in LC-ACC connectivity correlated negatively with depression severity (i.e., Geriatric Depression Scale and number of recurrences). Reduced connectivity of the LC during oddball performance seems to specifically characterize patients with late-life MDD, but not other populations of aged individuals with cognitive alterations. Such alteration is associated with different measures of disease severity, such as the current presence of symptoms and the burden of disease (number of recurrences)

Hospitalización a domicilio para pacientes quirúrgicos ante una pandemia por SARS-CoV-2: nuestra experiencia

Introduction: The HaDQ is an alternative to conventional hospitalization for clinically stable surgical patients who require complex nursing procedures due to intensity, frequency or characteristics, and control by a surgical specialist at home. Method: Cross-sectional, descriptive and retrospective study of the HADQ activity of our hospital during the first six months of 2020, to analyze the impact of the SARSCov2 pandemic in the unit. Three periods are distinguished: pre-pandemic (Jan-Feb), lockdown (Mar-Apr), post-lockdown (May-Jun). Two groups are differentiated: A (conventional HaD) and B (COVID19 preoperative screening). Various variables were collected: month, type, stay (HaD and hospital), procedures, readmissions, address, type of visits, covid+. A quantitative and qualitative descriptive statistical analysis of the results obtained was carried out. Results: 345 patients were admitted, 225 in group A (phase Pre (34%), Phase C (40%), and phase Post (25%)), and 120 in group B (Phase C (75%), phase Post (25%)). %)). The confinement (phase C) was the most active period of the HADQ, both due to the number of admissions (53%), and the complexity of group A, which required more procedures (71%) and more home visits (52%). There was also an increase in patients from the non-coverage area (42%), which involved medical and nursing visits at the Day Hospital (HD) (21%), and an increase in medical telephone consultations (36%). In the phase Post, the income of group A decreased by 37%. Conclusions: The HaDQ was reorganized due to the pandemic to care for more surgical patients, being an essential care resource, especially during confinement.Introducción: La hospitalización a domicilio para pacientes quirúrgicos (HaDQ) es una alternativa a la hospitalización convencional para pacientes quirúrgicos estables clínicamente, que precisen procedimientos de enfermería complejos por intensidad, frecuencia o características, y control por especialista quirúrgico en el domicilio. Método: Estudio transversal, descriptivo y retrospectivo de la actividad de la HADQ de nuestro hospital durante los primeros seis meses del 2020, para analizar la repercusión de la pandemia por SARS-CoV-2 en la unidad. Se distinguen tres periodos: prepandemia (enero-febreo), confinamiento (marzo-abril), posconfinamiento (mayo-junio). Se diferencian dos grupos: A (HaD convencional) y B (despistaje preoperatorio COVID19). Se recogieron diversas variables: mes, tipo, estancia (HaD y hospital), procedimientos, reingresos, domicilio, tipo visitas, COVID+. Se realizó un análisis estadístico descriptivo cuantitativo y cualitativo de los resultados obtenidos Resultados: Ingresaron 345 pacientes, 225 en el grupo A (fase Pre (34%), fase C (40%), y fase Pos (25%)), y 120 en el B (fase C (75%), fase Pos (25%)). El confinamiento (fase C) fue el período más activo de la HADQ, tanto por número de ingresos (53%), como por la complejidad del grupo A que requería más procedimientos (71%) y más visitas domiciliarias (52%). También aumentaron los pacientes de zona de no cobertura (42%), que implicaron visitas médicas y de enfermería en Hospital de Día (HD) (21%), y aumento de consultas telefónicas médicas (36%). En la fase Pos disminuyeron un 37% los ingresos del grupo A. Conclusiones: La HaDQ se reorganizó por la pandemia para atender a más pacientes quirúrgicos, siendo un recurso asistencial esencial, especialmente durante el confinamiento

Prevalence of dementia and major dementia subtypes in Spanish populations: A reanalysis of dementia prevalence surveys, 1990-2008

Background This study describes the prevalence of dementia and major dementia subtypes in Spanish elderly. Methods We identified screening surveys, both published and unpublished, in Spanish populations, which fulfilled specific quality criteria and targeted prevalence of dementia in populations aged 70 years and above. Surveys covering 13 geographically different populations were selected (prevalence period: 1990-2008). Authors of original surveys provided methodological details of their studies through a systematic questionnaire and also raw age-specific data. Prevalence data were compared using direct adjustment and logistic regression. Results The reanalyzed study population (aged 70 year and above) was composed of Central and North-Eastern Spanish sub-populations obtained from 9 surveys and totaled 12,232 persons and 1,194 cases of dementia (707 of Alzheimer's disease, 238 of vascular dementia). Results showed high variation in age- and sex-specific prevalence across studies. The reanalyzed prevalence of dementia was significantly higher in women; increased with age, particularly for Alzheimer's disease; and displayed a significant geographical variation among men. Prevalence was lowest in surveys reporting participation below 85%, studies referred to urban-mixed populations and populations diagnosed by psychiatrists. Conclusion Prevalence of dementia and Alzheimer's disease in Central and North-Eastern Spain is higher in females, increases with age, and displays considerable geographic variation that may be method-related. People suffering from dementia and Alzheimer's disease in Spain may approach 600,000 and 400,000 respectively. However, existing studies may not be completely appropriate to infer prevalence of dementia and its subtypes in Spain until surveys in Southern Spain are conductedFinancial aid was obtained from the Spanish RECSP C03-09, CIEN C03-06 and CIBERNED networks, and from the Pfizer Foundation in particularS

Stroke prevalence among the Spanish elderly: an analysis based on screening surveys

BACKGROUND: This study sought to describe stroke prevalence in Spanish elderly populations and compare it against that of other European countries. METHODS: We identified screening surveys -both published and unpublished- in Spanish populations, which fulfilled specific quality requirements and targeted prevalence of stroke in populations aged 70 years and over. Surveys covering seven geographically different populations with prevalence years in the period 1991–2002 were selected, and the respective authors were then asked to provide descriptions of the methodology and raw age-specific data by completing a questionnaire. In addition, five reported screening surveys in European populations furnished useful data for comparison purposes. Prevalence data were combined, using direct adjustment and logistic regression. RESULTS: The overall study population, resident in central and north-eastern Spain, totalled 10,647 persons and yielded 715 cases. Age-adjusted prevalences, using the European standard population, were 7.3% for men, 5.6% for women, and 6.4% for both sexes. Prevalence was significantly lower in women, OR 0.79 95% CI 0.68–0.93, increased with age, particularly among women, and displayed a threefold spatial variation with statistically significant differences. Prevalences were highest, 8.7%, in suburban, and lowest, 3.8%, in rural populations. Compared to pooled Spanish populations, statistically significant differences were seen in eight Italian populations, OR 1.39 95%CI (1.18–1.64), and in Kungsholmen, Sweden, OR 0.40 95%CI (0.27–0.58). CONCLUSION: Prevalence in central and north-eastern Spain is higher in males and in suburban areas, and displays a threefold geographic variation, with women constituting the majority of elderly stroke sufferers. Compared to reported European data, stroke prevalence in Spain can be said to be medium and presents similar age- and sex-specific traits

[Carta a Ignacio Hernando de Larramendi y Montiano]

Información adicional de autor de la carta: Director del Secretariat de Bens Immobles de l'ArquebisbatFotografía número: 76