Dementia-related genetic variants in an Italian population of early-onset Alzheimer’s disease

Early-onset Alzheimer’s disease (EOAD) is the most common form of early-onset dementia. Although three major genes have been identified as causative, the genetic contribution to the disease remains unsolved in many patients. Recent studies have identified pathogenic variants in genes representing a risk factor for developing Alzheimer’s disease (AD) and in causative genes for other degenerative dementias as responsible for EOAD. To study them further, we investigated a panel of candidate genes in 102 Italian EOAD patients, 45.10% of whom had a positive family history and 21.74% with a strong family history of dementia. We found that 10.78% of patients carried pathogenic or likely pathogenic variants, including a novel variant, in PSEN1, PSEN2, or APP, and 7.84% showed homozygosity for the ε4 APOE allele. Additionally, 7.84% of patients had a moderate risk allele in PSEN1, PSEN2, or TREM2 genes. Besides, we observed that 12.75% of our patients carried only a variant in genes associated with other neurodegenerative diseases. The combination of these variants contributes to explain 46% of cases with a definite familiarity and 32% of sporadic forms. Our results confirm the importance of extensive genetic screening in EOAD for clinical purposes, to select patients for future treatments and to contribute to the definition of overlapping pathogenic mechanisms between AD and other forms of dementia

Structural analysis on mutation residues and interfacial water molecules for human TIM disease understanding

10.1186/1471-2105-14-S16-S11BMC Bioinformatics14SUPPL16-BBMI

Assessment of the health status in the Massa Lombarda cohort: a preliminary description of the program evaluating cardio-cerebro-vascular disease risk factors and quality of life in an elderly population.

he Massa Lombarda program (MLP) is the first step of a European multi-center program, promoted and coordinated from Bologna University's Academic Spin off Health Research and Development, which attempts to manage advanced sanitary research in general population. The instant individual definition (IID) study is the first phase of the program concerning the study of risk factors (RF) and early diagnosis of coronary heart disease (CHD), through a new diagnostic technology called myocardial perfusion scoring system (MPS). The study consists of a longitudinal observational epidemiological investigation of adult population (above 25 years of age) resident in Massa Lombarda (Ravenna), with the survey of social and biological parameters. The elderly part of the population (1000 subjects above 75 years) was submitted to a more complex analysis, as part of the study on health status in European aging populations, aimed at revealing the determinants influencing the healthy aging, and at identifying their impact on mortality,cardiovascular and respiratory morbidity, disability and decline of quality of life. Laboratory analyses were aimed at identifying the following factors: (i) Genetic markers related to pro and anti-inflammatory cytokine- codifying genes. (ii) Oxidative stress-involved molecules, and inflammation-involved genes, and more in general genes involved in the brittleness(iii) (ApoE). Appraising the degree of interaction with non-genetic factors, like measurable immunological markers in the peripheral blood, markers of reactions to oxidative stress,evaluation of metabolic parameters. Moreover, old population is expected to answer the questionnaires for evaluation of the dietary habits, physical activity, self-sufficiency,cognitive ability, motor coordination, perceived stress and social relationships

Prevalence of Hypo- and Hyperalphalipoproteinemia according to different diagnostic criteria in the massa lombarda project cohort

Objective: Several studies use different cut off point to define the pathological HDL-C levels. We applied the most cited diagnostic criteria to the Massa Lombaxda Project cohort in order to estimate the prevalence of Hypo (HypoALP)- and Hyperalphalipoproteinemia (HyperALP). Methods: We stratified our sample (1199 adult subjects M:516, F:683) from The Massa Lombaxda Project cohort according to the main diagnostic criteria: the first one was based on the cut-off < 10th percentile for hypoALP and >90th percentile for hyperALP; the second one was based on NCEP (National Cholesterol Education Program) ATPIII (Adult Treatment Panel III) cut-off <40 mg/dl for low HDL-C levels and _>60 mg/dl for high HDL-C levels; the third one from Omagari Study was based on the cut off _>80 < 100 mg/dl for HyperALP and _> 100 mg/dl for marked HyperALP. Results: According to the first cut-off point the prevalence values of Hypo- Normo- and HyperALP were respectively F:5.1% M:3.5%, F:46.1% M:35.2%, F:5.6% M:4.2%; according to the second cut off point the values were F:6.0% M:12.8%, F:27.3% M:23.7%, F:23.5% M:6.4%; according to the third cut off point the prevalence values of Hyper- and marked HyperALP were F:3.5% M:0.5%, F:0.1% M:0.0%. Conclusion: Our research showed that the prevalence of Hypo- Normoand HyperALP in this sample changes according to the cut off point that we used; further according to ATP III diagnostic criteria there were more men (9.3%) with a significant cardiovascular risk factor: low HDL-C levels. It could be suitable to standardize the diagnostic methods

"Biological identikit": development of a SNPs-panel for the analysis of forensic DNA phenotyping and ancestry

The need to identify victims of mass disasters and perpetrators of crimes is fundamental for humanitarian, ethical and legal reasons. Individuals, whose genetic profiles are not yet known to investigators, cannot be identified by standard forensic DNA analysis. To date, technological progress allows for the analysis of Forensic DNA Phenotyping (FDP) which provides for the definition of Externally Visible Features (EVCs); and the analysis of the biogeographical ancestry (BGA), which allows to define the ancestral origin. The aim of this study was to evaluate the potential of a new panel of about 900 SNPs in predicting phenotypic traits and biogeographical origin. Recent biological material was analysed and subsequently the analysis was extended to include evidence found at the crime scene or extracted DNA, both preserved for long periods of time. The goal was to create a "biological identikit", useful for determining the phenotypic characteristics of unknown corpses and directing investigators to alleged victims or relatives or in a crime to narrow the circle of suspects. The panel consists of 41 SNPs for phenotyping and 850 SNPs for ancestry. It was tested on 8 recent samples and 26 samples extracted and stored for a long time. All the 891 SNPs were successfully incorporated into a single two-step multiplex PCR reaction using the IonAmpliSeq ™ Library Plus and applied for massive parallel sequencing with the Ion S5 platform using up to 0.05 ng / µl of DNA. The analysis of the results was carried out with an in-house predictive algorithm and by consulting 20 databases containing population frequencies. By comparing the results obtained with identikit or video-photographic surveys, it was possible to predict the phenotype and ancestry with an accuracy more than 90%. Although these new markers are unable to identify an individual, they can be a valuable investigative tool useful for personal identification

Unusual Tissues and Sample Collection Strategies on Exhumed Bodies

The choice of soft or hard tissues to be sampled in case of exhumation of corpses for identification purposes or family relationship testing is based on the degradation conditions of the corpse: the more the corpse is degraded, the less DNA is expected to be retrieved from soft tissue. Therefore, the choice of the \u201cbest\u201d tissue samples usually falls on teeth and bones in these \u201cdifficult\u201d cases, even though the DNA extraction procedure requires time and effort and it can often result in unexpected, negative results. We here present the results of a daily practice survey that shows that it is possible to obtain good results even on DNA extracted from tissues that appear to be less \u201cappealing\u201d to the examiner by performing \u201csimple\u201d corneal/scleral swabs along with cartilage. While DNA extracted from cartilage has been already described, to our knowledge there is no evidence of publications in the scientific literature dealing with cornea/sclera as a source of DNA in the forensic laboratory. The obtained results demonstrate that it may be advisable to consider other tissues which bear the potential of returning good profile results despite not appearing particularly useful and better control of contamination