Towards a Common Approach for Mapping Areas Susceptible to Landslides in Europe

In the framework of the European Soil Thematic Strategy, and the associated preparation of a directive on the protection and sustainable use of soil, landslides were recognized as a soil threat requiring specific strategies for risk assessment and management. The criteria for harmonized risk area delineation proposed by the Soil Information Working Group (SIWG) of the European Soil Bureau Network (ESBN) adopt a nested geographical approach based on �Tiers� and exploit thematic and environmental data of different type, quality, and resolution using a variety of methodological and technological approaches. The Tier 1 assessment is aimed at the general (i.e., synoptic) identification of areas potentially subject to landslides, providing a low-resolution (1:1 Million scale) evaluation of landslide threats using existing thematic and environmental data. The Tier 2 assessment is intended to perform more detailed analyses in the areas identified by Tier 1, and should provide results at a higher spatial resolution using existing and new data currently not available in all European countries. The main requirement for a Tier 1 assessment for the delineation of areas subject to soil threats in Europe is the availability of relevant input data. At present, a continent-wide assessment of landslide susceptibility in Europe is feasible only adopting a qualitative evaluation technique. This is largely because a systematic landslide inventory coverage is not yet available for the whole of Europe. A generic Tier 1 landslide susceptibility assessment can thus be performed using a reduced set of data, including common information on the instability conditioning factors (e.g. soil/bedrock, slope angle and land cover). Adoption of an index-based evaluation method can allow the production of a continent-wide landslide susceptibility map for Europe, provided it is calibrated with representative landslide data. Quantitative evaluations of landslide susceptibility according to a Tier 2 assessment require the availability of landslide inventory maps and databases. The minimum content requirement for such databases to generate Tier 2 susceptibility maps at scales around 1:200,000 consists of type and location of historical landslide events. When these data are available in addition to ground material and other conditioning factor data, multivariate statistical evaluation techniques can be applied to quantify landslide susceptibility of appropriate terrain-mapping units. These might best consist of small administrative units in order to meet the needs of most end-users. We outline the current advances towards the development of a common methodology for assessing the landslide threat in Europe. We refer to limitations, data needs and future work to be carried out, and present examples of preliminary assessments.JRC.H.7 - Land management and natural hazard

Mutations in MAPT give rise to aneuploidy in animal models of tauopathy

Tau is a major microtubule-associated protein in brain neurons. Its misfolding and accumulation cause neurodegenerative diseases characterized by brain atrophy and dementia, named tauopathies. Genetic forms are caused by mutations of microtubule-associated protein tau gene (MAPT). Tau is expressed also in nonneural tissues such as lymphocytes. Tau has been recently recognized as a multifunctional protein, and in particular, some findings supported a role in genome stability. In fact, peripheral cells of patients affected by frontotemporal dementia carrying different MAPT mutations showed structural and numerical chromosome aberrations. The aim of this study was to assess chromosome stability in peripheral cell from two animal models of genetic tauopathy, JNPL3 and PS19 mouse strains expressing the human tau carrying the P301L and P301S mutations, respectively, to confirm the previous data on humans. After demonstrating the presence of mutated tau in spleen, we performed standard cytogenetic analysis of splenic lymphocytes from homozygous and hemizygous JNPL3, hemizygous PS19, and relevant controls. Losses and gains of chromosomes (aneuploidy) were evaluated. We detected a significantly higher level of aneuploidy in JNPL3 and PS19 than in control mice. Moreover, in JNPL3, the aneuploidy was higher in homozygotes than in hemizygotes, demonstrating a gene dose effect, which appeared also to be age independent. Our results show that mutated tau is associated with chromosome instability. It is conceivable to hypothesize that in genetic tauopathies the aneuploidy may be present also in central nervous system, possibly contributing to neurodegeneration

Tau mutations serve as a novel risk factor for cancer

In addition to its well-recognized role in neurodegeneration, tau participates in maintenance of genome stability and chromosome integrity. In particular, peripheral cells from patients affected by frontotemporal lobar degeneration carrying a mutation in tau gene (genetic tauopathies), as well as cells from animal models, show chromosome numerical and structural aberrations, chromatin anomalies, and a propensity toward abnormal recombination. As genome instability is tightly linked to cancer development, we hypothesized that mutated tau may be a susceptibility factor for cancer. Here we conducted a retrospective cohort study comparing cancer incidence in families affected by genetic tauopathies to control families. Additionally, we carried out a bioinformatics analysis to highlight pathways associated with the tau protein interactome. We report that the risk of developing cancer is significantly higher in families affected by genetic tauopathies, and a high proportion of tau protein interactors are involved in cellular processes particularly relevant to cancer. These findings disclose a novel role of tau as a risk factor for cancer, providing new insights in the various pathological roles of mutated tau

A novel missense mutation in PSEN2 gene associated with a clinical phenotype of frontotemporal dementia

Background: In Familial Alzheimer's disease defects in three genes - the amyloid precursors protein (APP) gene on chromosome 21, the presenilin 1 (PSEN1) gene on chromosome 14 and the presenilin 2 (PSEN2) on chromosome 1- have been identified. More than 160 pathogenic missense mutations have been described in PSEN1, with wide clinic phenotypic variability. In PSEN2 only 11 missense mutations are known, in two of which (M239V and T122R) the clinical phenotype may be frontotemporal dementia-like. Methods: We present a novel PSEN2 mutation (Y231C) in an Italian patient who seven years ago, at age 55, manifested mood and behavioural disorders characterized by apathia, delusions, physical aggressive behaviour and psychomotor agitation. Language disturbances appeared one year later and mild memory loss three years later. The neuropsychological pattern suggested a main dysfunction in posterior temporal and parietal cortex. MRI showed diffuse atrophy, especially in posterior regions. Results: The genetic study showed an A-to-G mutation in exon seven of PSEN2 gene, resulting in tyrosine to cysteine substitution at residue 231. Conclusions: This new mutation confirms the variability of the phenotypes associated with PSEN2 mutations and justified the analysis of this gene in behavioural disturbances associated with degenerative dementia, at least in Italy in which PSEN2 mutations seems more frequent than in other countries

Consensus classification of human prion disease histotypes allows reliable identification of molecular subtypes: an inter-rater study among surveillance centres in Europe and USA

The current classification of human sporadic prion diseases recognizes six major phenotypic subtypes with distinctive clinicopathological features, which largely correlate at the molecular level with the genotype at the polymorphic codon 129 (methionine, M, or valine, V) in the prion protein gene and with the size of the protease-resistant core of the abnormal prion protein, PrP(Sc) (i.e. type 1 migrating at 21 kDa and type 2 at 19 kDa). We previously demonstrated that PrP(Sc) typing by Western blotting is a reliable means of strain typing and disease classification. Limitations of this approach, however, particularly in the interlaboratory setting, are the association of PrP(Sc) types 1 or 2 with more than one clinicopathological phenotype, which precludes definitive case classification if not supported by further analysis, and the difficulty of fully recognizing cases with mixed phenotypic features. In this study, we tested the inter-rater reliability of disease classification based only on histopathological criteria. Slides from 21 cases covering the whole phenotypic spectrum of human sporadic prion diseases, and also including two cases of variant Creutzfeldt-Jakob disease (CJD), were distributed blindly to 13 assessors for classification according to given instructions. The results showed good-to-excellent agreement between assessors in the classification of cases. In particular, there was full agreement (100 %) for the two most common sporadic CJD subtypes and variant CJD, and very high concordance in general for all pure phenotypes and the most common subtype with mixed phenotypic features. The present data fully support the basis for the current classification of sporadic human prion diseases and indicate that, besides molecular PrP(Sc) typing, histopathological analysis permits reliable disease classification with high interlaboratory accuracy

Detection of prions in blood from patients with variant Creutzfeldt-Jakob disease

Prions can be detected in blood from patients with variant Creutzfeldt-Jakob disease with high sensitivity and specificity.</jats:p

Constant Transmission Properties of Variant Creutzfeldt-Jakob Disease in 5 Countries

Variant Creutzfeldt-Jakob disease (vCJD) has been reported in 12 countries. We hypothesized that a common strain of agent is responsible for all vCJD cases, regardless of geographic origin. To test this hypothesis, we inoculated strain-typing panels of wild-type mice with brain material from human vCJD case-patients from France, the Netherlands, Italy, and the United States. Mice were assessed for clinical disease, neuropathologic changes, and glycoform profile; results were compared with those for 2 reference vCJD cases from the United Kingdom. Transmission to mice occurred from each sample tested, and data were similar between non-UK and UK cases, with the exception of the ranking of mean clinical incubation times of mouse lines. These findings support the hypothesis that a single strain of infectious agent is responsible for all vCJD infections. However, differences in incubation times require further subpassage in mice to establish any true differences in strain properties between cases

Clinical phenotypic variability in an Italian family bearing the IVS6+ 5_8delGTGA mutation in PGRN gene

Background Frontotemporal dementia (FTD) is a complex presenile disorder characterized by behavioural changes and executive functions, expression of fronto-temporal degeneration. Hereditary FTD accounts for 20-30% of cases and, in the past decade, mutations in the microtubule associated protein tau (MAPT)gene were identified as a main genetic causes of familial FTD. In 2006, mutations in the gene encoding progranulin (PGRN) were reported, to account for a wide part of the familial FTD cases. Clinically, an high phenotypic variability within and among the kindreds is reported in the familial FTD associated with PGRN mutations and occasionally the memory deficits are the first symptoms, resembling Alzheimer's disease (AD). We report an Italian family with dementia associated with a PGRN mutation characterized by a deletion of 4 base pairs inside the intron 6 of the gene, leading to haploin sufficiency In our kindred, all three affected patients carried the mutation, but presented very different clinical phenotypes, evoking FTD, AD and rapidly-progressive dementia mimicking prion disease. Methods Informations on the members of the first, second and third generations were obtained conducting interviews with relatives, while for the three patients studied, the clinical evidence of dementia symptoms and their characterization was documented directly with sequential neurological examinations, cognitive assessments and neuroimaging. Blood sample collection and DNA extraction from peripheral blood lymphocytes for genetic analysis were performed after written informed consent of the patients. Results In our pedigree, the PGRN mutated patients are affected by dementia with three different clinical pictures: FTD, AD and rapidly progressive dementia mimicking prion disease. Neuropsychological examinations supported these diagnoses, documenting generalized deficits of cortical functions in AD patient and deficits in executive functions and in language in FTD patient. Regarding neuroimaging, in the same two cases MRI results do not correspond to the clinical diagnosis. Conclusions These findings confirms the marked heterogeneity of the clinico-radiological features in patients with PGNR mutations and underline the need of considering mutations of this gene as causes of familial dementing diseases with atypical or uncommon features or discrepancies between the clinical and the neuroimaging findings