PARTICIPATION MOTIVATION AMONG YOUNG SOCCER ATHLETES: RESEARCH EVIDENCE FROM GREECE

The purpose of this study was to determine participation motives of youth soccer players and to examine their participation motives with regard to their age, sport experience, and training volume levels. The sample of this empirical research consisted of 171 young soccer athletes from 16 different soccer teams, all located in the prefecture of Ilia, Western Greece. The well-known sports participation motivation questionnaire (PMQ) was used. Analysis of data was conducted by the use non-parametric k-independent-samples t-tests. The results showed that among the components of the sports participation motivation, significant differences were observed for the aspects of achievement and the aspect of finding friendship. No other significant differences were found. The results of this study confirm that sport experience and the athletes’ age is effective in motivating athletes' continuation and commitment to their physical activity. Article visualizations

Neuroanatomical Correlates of Intelligence in Healthy Young Adults: The Role of Basal Ganglia Volume

Background: In neuropsychiatric diseases with basal ganglia involvement, higher cognitive functions are often impaired. In this exploratory study, we examined healthy young adults to gain detailed insight into the relationship between basal ganglia volume and cognitive abilities under non-pathological conditions. Methodology/Principal Findings: We investigated 137 healthy adults that were between the ages of 21 and 35 years with similar educational backgrounds. Magnetic resonance imaging (MRI) was performed, and volumes of basal ganglia nuclei in both hemispheres were calculated using FreeSurfer software. The cognitive assessment consisted of verbal, numeric and figural aspects of intelligence for either the fluid or the crystallised intelligence factor using the intelligence test Intelligenz-Struktur- Test (I-S-T 2000 R). Our data revealed significant correlations of the caudate nucleus and pallidum volumes with figural and numeric aspects of intelligence, but not with verbal intelligence. Interestingly, figural intelligence associations were dependent on sex and intelligence factor;in females, the pallidum volumes were correlated with crystallised figural intelligence (r=0.372, p=0.01),whereas in males, the caudate volumes were correlated with fluid figural intelligence (r=0.507, p=0.01). Numeric intelligence was correlated with right-lateralised caudate nucleus volumes for both females and males, but only for crystallised intelligence (r=0.306, p=0.04 and r=0.459, p=0.04, respectively). The associations were not mediated by prefrontal cortical subfield volumes when controlling with partial correlation analyses. Conclusions/Significance: The findings of our exploratory analysis indicate that figural and numeric intelligence aspects, but not verbal aspects, are strongly associated with basal ganglia volumes. Unlike numeric intelligence, the type of figural intelligence appears to be related to distinct basal ganglia nuclei in a sex-specific manner. Subcortical brain structures thus may contribute substantially to cognitive performance

Multivariate and Univariate Neuroimaging Biomarkers of Alzheimer's Disease

We performed univariate and multivariate discriminant analysis of FDG-PET scans to evaluate their ability to identify Alzheimer's disease (AD). FDG-PET scans came from two sources: 17 AD patients and 33 healthy elderly controls were scanned at the University of Michigan; 102 early AD patients and 20 healthy elderly controls were scanned at the Technical University of Munich, Germany. We selected a derivation sample of 20 AD patients and 20 healthy controls matched on age with the remainder divided into 5 replication samples. The sensitivity and specificity of diagnostic AD-markers and threshold criteria from the derivation sample were determined in the replication samples. Although both univariate and multivariate analyses produced markers with high classification accuracy in the derivation sample, the multivariate marker's diagnostic performance in the replication samples was superior. Further, supplementary analysis showed its performance to be unaffected by the loss of key regions. Multivariate measures of AD utilize the covariance structure of imaging data and provide complementary, clinically relevant information that may be superior to univariate measures

Cerebrospinal Fluid BACE1 Activity and Brain Amyloid Load in Alzheimer's Disease

The secretase BACE1 is fundamentally involved in the development of cerebral amyloid pathology in Alzheimer's disease (AD). It has not been studied so far to what extent BACE1 activity in cerebrospinal fluid (CSF) mirrors in vivo amyloid load in AD. We explored associations between CSF BACE1 activity and fibrillar amyloid pathology as measured by carbon-11-labelled Pittsburgh Compound B positron emission tomography ([11C]PIB PET). [11C]PIB and CSF studies were performed in 31 patients with AD. Voxel-based linear regression analysis revealed significant associations between CSF BACE1 activity and [11C]PIB tracer uptake in the bilateral parahippocampal region, the thalamus, and the pons. Our study provides evidence for a brain region-specific correlation between CSF BACE1 activity and in-vivo fibrillar amyloid pathology in AD. Associations were found in areas close to the brain ventricles, which may have important implications for the use of BACE1 in CSF as a marker for AD pathology and for antiamyloid treatment monitoring

The Common Acid Sphingomyelinase Polymorphism p.G508R is Associated with Self-Reported Allergy

Background: Acid sphingomyelinase (ASM) is a key regulator of ceramide-dependent signalling pathways. Among others, activation of ASM can be induced by CD95 or cytokine signalling and by cellular stress resulting from inflammation or infection. Increased ASM activity was observed in a variety of human diseases including inflammatory and neuropsychiatric disorders. We hypothesized that basal ASM activity might influence the susceptibility for common human diseases. Methods: The general health condition of 100 young people was assessed using a questionnaire. The ASM polymorphism rs1050239 (c.1522G>A;encoding p.G508R) was determined from genomic DNA. Activities of secretory (S-) and lysosomal (L-) ASM were measured in blood plasma and peripheral blood cells respectively. Results: The polymorphism rs1050239 was significantly associated with self-reported allergy (p=4.68x10(-4);adjusted p-value for multiple testing 0.007). Allergy was more prevalent in carriers of the minor A allele compared to non-carriers (p=0.00015;odds ratio=6.5, 95% CI 2.15-21.7). S-ASM activity was significantly associated with rs1050239 (p=5.3x10(-7)) and decreased with the number of A alleles in a gene-dosage dependent manner. In allergic patients, S-ASM activity was moderately decreased (p=0.034). L-ASM activity was significantly lower in subjects homozygous for the minor A allele (p=0.025) but not different between allergic and non-allergic subjects (p=0.318). Conclusion: Our analysis provides evidence for an involvement of ASM in the pathophysiology of allergy, which is in line with previous reports addressing the role of sphingolipids in this disorder. Further studies should clarify the mechanism linking rs1050239 to allergy. The ASM pathway might be useful for predicting allergic disposition and disease course and as a therapeutic target. Copyright (C) 2014 S. Karger AG, Base

Influence of brain-derived neurotrophic factor and apolipoprotein E genetic variants on hemispheric and lateral ventricular volume of young healthy adults

Objective: Brain-derived neurotrophic factor (BDNF) and apolipoprotein E (ApoE) are thought to be implicated in a variety of neuronal processes, including cell growth, resilience to noxious stimuli and synaptic plasticity. A Val to Met substitution at codon 66 in the BDNF protein has been associated with a variety of neuropsychiatric conditions. The ApoE4 allele is considered a risk factor for late-onset Alzheimer's disease, but its effects on young adults are less clear. We sought to investigate the effects of those two polymorphisms on hemispheric and lateral ventricular volumes of young healthy adults. Methods: Hemispheric and lateral ventricular volumes of 144 healthy individuals, aged 19–35 years, were measured using high resolution magnetic resonance imaging and data were correlated with BDNF and ApoE genotypes. Results: There were no correlations between BDNF or ApoE genotype and hemispheric or lateral ventricular volumes. Conclusion: These findings indicate that it is unlikely that either the BDNF Val66Met or ApoE polymorphisms exert any significant effect on hemispheric or lateral ventricular volume. However, confounding epistatic genetic effects as well as relative insensitivity of the volumetric methods used cannot be ruled out. Further imaging analyses are warranted to better define any genetic influence of the BDNF Val6Met and ApoE polymorphism on brain structure of young healthy adults

Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration

Mutations in the gene coding for Sequestosome 1 (SQSTM1) have been genetically associated with amyotrophic lateral sclerosis (ALS) and Paget disease of bone. In the present study, we analyzed the SQSTM1 coding sequence for mutations in an extended cohort of 1,808 patients with frontotemporal lobar degeneration (FTLD), ascertained within the European Early-Onset Dementia consortium. As control dataset, we sequenced 1,625 European control individuals and analyzed whole-exome sequence data of 2,274 German individuals (total n = 3,899). Association of rare SQSTM1 mutations was calculated in a meta-analysis of 4,332 FTLD and 10,240 control alleles. We identified 25 coding variants in FTLD patients of which 10 have not been described. Fifteen mutations were absent in the control individuals (carrier frequency < 0.00026) whilst the others were rare in both patients and control individuals. When pooling all variants with a minor allele frequency < 0.01, an overall frequency of 3.2 % was calculated in patients. Rare variant association analysis between patients and controls showed no difference over the whole protein, but suggested that rare mutations clustering in the UBA domain of SQSTM1 may influence disease susceptibility by doubling the risk for FTLD (RR = 2.18 [95 % CI 1.24-3.85]; corrected p value = 0.042). Detailed histopathology demonstrated that mutations in SQSTM1 associate with widespread neuronal and glial phospho-TDP-43 pathology. With this study, we provide further evidence for a putative role of rare mutations in SQSTM1 in the genetic etiology of FTLD and showed that, comparable to other FTLD/ALS genes, SQSTM1 mutations are associated with TDP-43 pathology

TBK1 mutation spectrum in an extended European patient cohort with frontotemporal dementia and amyotrophic lateral sclerosis

We investigated the mutation spectrum of the TANK-Binding Kinase 1 (TBK1) gene and its associated phenotypic spectrum by exonic resequencing of TBK1 in a cohort of 2,538 patients with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), or FTD plus ALS, ascertained within the European Early-Onset Dementia Consortium. We assessed pathogenicity of predicted protein-truncating mutations by measuring loss of RNA expression. Functional effect of in-frame amino acid deletions and missense mutations was further explored in vivo on protein level and in vitro by an NFB-induced luciferase reporter assay and measuring phosphorylated TBK1. The protein-truncating mutations led to the loss of transcript through nonsense-mediated mRNA decay. For the in-frame amino acid deletions, we demonstrated loss of TBK1 or phosphorylated TBK1 protein. An important fraction of the missense mutations compromised NFB activation indicating that at least some functions of TBK1 are lost. Although missense mutations were also present in controls, over three times more mutations affecting TBK1 functioning were found in the mutation fraction observed in patients only, suggesting high-risk alleles (P = 0.03). Total mutation frequency for confirmed TBK1 LoF mutations in the European cohort was 0.7%, with frequencies in the clinical subgroups of 0.4% in FTD, 1.3% in ALS, and 3.6% in FTD-ALS

Deleterious ABCA7 mutations and transcript rescue mechanisms in early onset Alzheimer's disease

Altres ajuts: The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The research was funded in part by the European Commission Seventh Framework Programme for research, technological development, and demonstration under grant agreement 305299 (AgedBrainSYSBIO), the Belgian Science Policy Office Interuniversity Attraction Poles program, the Alzheimer Research Foundation (SAO-FRA), the Flemish government-initiated Flanders Impulse Program on Networks for Dementia Research (VIND), the Flemish government-initiated Methusalem Excellence Program, the Research Foundation Flanders (FWO), the VIB Technology Fund, the University of Antwerp Research Fund, Belgium; European Regional Development Fund, the Italian Ministry of Health (Ricerca Corrente and RF-2010-2319722), and the Fondazione Cassa di Risparmio di Pistoia e Pescia grant (2014.0365).Premature termination codon (PTC) mutations in the ATP-Binding Cassette, Sub-Family A, Member 7 gene (ABCA7) have recently been identified as intermediate-to-high penetrant risk factor for late-onset Alzheimer's disease (LOAD). High variability, however, is observed in downstream ABCA7 mRNA and protein expression, disease penetrance, and onset age, indicative of unknown modifying factors. Here, we investigated the prevalence and disease penetrance of ABCA7 PTC mutations in a large early onset AD (EOAD)-control cohort, and examined the effect on transcript level with comprehensive third-generation long-read sequencing. We characterized the ABCA7 coding sequence with next-generation sequencing in 928 EOAD patients and 980 matched control individuals. With MetaSKAT rare variant association analysis, we observed a fivefold enrichment (p = 0.0004) of PTC mutations in EOAD patients (3%) versus controls (0.6%). Ten novel PTC mutations were only observed in patients, and PTC mutation carriers in general had an increased familial AD load. In addition, we observed nominal risk reducing trends for three common coding variants. Seven PTC mutations were further analyzed using targeted long-read cDNA sequencing on an Oxford Nanopore MinION platform. PTC-containing transcripts for each investigated PTC mutation were observed at varying proportion (5-41% of the total read count), implying incomplete nonsense-mediated mRNA decay (NMD). Furthermore, we distinguished and phased several previously unknown alternative splicing events (up to 30% of transcripts). In conjunction with PTC mutations, several of these novel ABCA7 isoforms have the potential to rescue deleterious PTC effects. In conclusion, ABCA7 PTC mutations play a substantial role in EOAD, warranting genetic screening of ABCA7 in genetically unexplained patients. Long-read cDNA sequencing revealed both varying degrees of NMD and transcript-modifying events, which may influence ABCA7 dosage, disease severity, and may create opportunities for therapeutic interventions in AD