Association of antenatal and early childhood air pollution and greenspace exposures with respiratory pathogen upper airway acquisitions and respiratory health outcomes.

The association of air pollution and greenspace with respiratory pathogen acquisition and respiratory health was investigated in a community-based birth-cohort of 158 Australian children. Weekly nasal swabs and daily symptom-diaries were collected for 2-years, with annual reviews from ages 3-7-years. Annual exposure to fine-particulate-matter (PM2.5), nitrogen-dioxide (NO2), and normalised-difference-vegetation-index (NDVI) was estimated for pregnancy and the first 2-years-of-life. We examined rhinovirus, any respiratory virus, Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae detections in the first 3-months-of-life, age at initial pathogen detection, wheezing in the first 2-years, and asthma at ages 5-7-years. Our findings suggest that higher NDVI was associated with fewer viral and M. catarrhalis detections in the first 3-months, while increased PM2.5 and NO2 were linked to earlier symptomatic rhinovirus and H. influenzae detections, respectively. However, no associations were observed with wheezing or asthma. Early-life exposure to air pollution and greenspace may influence early-life respiratory pathogen acquisition and illness. .

Pediatric central venous access devices: practice, performance, and costs.

BACKGROUND: Healthcare delivery is reliant on a functional central venous access device (CVAD), but the knowledge surrounding the burden of pediatric CVAD-associated harm is limited. METHODS: A prospective cohort study at a tertiary-referral pediatric hospital in Australia. Children <18 years undergoing insertion of a CVAD were screened from the operating theatre and intensive care unit records, then assessed bi-weekly for up to 3 months. Outcomes were CVAD failure and complications, and associated healthcare costs (cost of complications). RESULTS: 163 patients with 200 CVADs were recruited and followed for 6993 catheter days, with peripherally inserted central catheters most common (n = 119; 60%). CVAD failure occurred in 20% of devices (n = 30; 95% CI: 15-26), at an incidence rate (IR) of 5.72 per 1000 catheter days (95% CI: 4.09-7.78). CVAD complications were evident in 43% of all CVADs (n = 86; 95% CI: 36-50), at a rate of 12.29 per 1000 catheter days (95% CI: 9.84-15.16). CVAD failure costs were A$826 per episode, and A$165,372 per 1000 CVADs. Comparisons between current and recommended practice revealed inconsistent use of ultrasound guidance for insertion, sub-optimal tip-positioning, and appropriate device selection. CONCLUSIONS: CVAD complications and failures represent substantial burdens to children and healthcare. Future efforts need to focus on the inconsistent use of best practices. IMPACT: Current surveillance of central venous access device (CVAD) performance is likely under-estimating actual burden on pediatric patients and the healthcare system. CVAD failure due to complication was evident in 20% of CVADs. Costs associated with CVAD complications average at $2327 (AUD, 2020) per episode. Further investment in key diverse practice areas, including new CVAD types, CVAD pathology-based occlusion and dislodgment strategies, the appropriate use of device types, and tip-positioning technologies, will likely lead to extensive benefit.

Epidemiology of respiratory syncytial virus in a community birth cohort of infants in the first 2 years of life.

Respiratory syncytial virus (RSV) is the most common virus identified in children hospitalised with acute respiratory infections. However, less is known about RSV in community settings. This report describes RSV epidemiology in the community, including acute illness episodes, healthcare burden, and risk factors in Australian children during the first 2-years of life. A community-based, birth cohort from Brisbane, Australia, followed children until their second birthday. Parents completed daily respiratory symptom and illness-burden diaries. Weekly parent-collected nasal swabs were analysed for RSV by real-time polymerase chain reaction assays. Serum RSV-neutralising antibodies were assayed at age 3 years. Overall, 158 children provided 11,216 swabs, of which 104 were RSV-positive (85 incident episodes). RSV incidence in the first 2 years of life was 0.46 (95% CI = 0.37-0.58) episodes per child-year. Incidence increased with age and formal childcare attendance and was highest in autumn. Of 82 episodes linked with symptom data, 60 (73.2%) were symptomatic, 28 (34.1%) received community-based medical care, and 2 (2.4%) led to hospitalisation. Viral load was higher in symptomatic than asymptomatic infections. In 72 children, RSV-specific antibody seroprevalence was 94.4% at age 3 years.Conclusion: RSV incidence increased after age 6-months with approximately three-quarters of infections symptomatic and most infections treated in the community. What is known •RSV is a major cause of hospitalisation for acute lower respiratory infections in infants and young children, especially in the first 6 months of life. •However, limited data exist on the overall burden in young children at the community level. What is new •RSV incidence in the community increases after age 6 months, and by 3 years, most children have been infected. •About one-quarter of RSV infections were asymptomatic in children aged < 2 years, and approximately 60% of children with RSV-related symptoms had a healthcare contact of any kind with most managed within the community.

The Frailty Index in centenarians and their offspring.

Frailty has been indicated as a way for capturing biological aging of the individual and Frailty Index (FI) may serve for this purpose. This study designed the FI in a cohort of centenarians, their offspring and control subjects sex- and age-matched with offspring. The FI mean value was 0.47 (SD 0.13) in centenarians, 0.15 (SD 0.12) in their offspring, and 0.22 (SD 0.14) in controls (p < 0.001). The difference between offspring and controls was statistically significant (p = 0.003). The correlation between FI and age was significant in offspring (r = 0.46, p < 0.001), close to significance in controls (r = 0.25, p = 0.08) and not significant in centenarians. Our study confirms that FI is a marker of biological age useful to discriminate different degrees of frailty even at extremely advanced age.

Increased expression of TREM2 in peripheral cells from mild cognitive impairment patients who progress into Alzheimer's disease.

BACKGROUND AND PURPOSE: Neuroinflammation plays a role in the aetiopathogenesis of Alzheimer's disease (AD). Triggering receptor expressed on myeloid cells 2 (TREM2), a cell surface receptor of the immunoglobulin superfamily, seems to have protective anti-inflammatory activity in AD. METHODS: Triggering receptor expressed on myeloid cells 2 expression was analysed in peripheral blood mononuclear cells from healthy subjects (CT) and from patients with either AD or mild cognitive impairment (MCI). MCI patients were re-evaluated at a 2-year follow-up to investigate their progression to AD (MCI-AD) or lack thereof (MCI-MCI). RESULTS: Triggering receptor expressed on myeloid cells 2 gene expression was higher in AD than CT patients, but was highest in MCI. At recruitment TREM2 levels were higher in MCI-AD than in MCI-MCI, and in MCI-AD were higher initially than at follow-up. TREM2 displayed a moderate degree of sensitivity and specificity for identifying MCI-AD in all MCI patients. Our data showed higher TREM2 levels in allele ε4 of apolipoprotein E (ApoE ε4) carriers than non-carriers in MCI and particularly in MCI-AD. CONCLUSIONS: These data seem to confirm the protective role of TREM2 in the pre-clinical stage of AD. Upregulation of TREM2 in MCI-AD could be a mechanism to counteract the activation of neuroinflammatory processes. It is possible that TREM2 and ApoE ε4 interact synergistically in the pre-clinical stage of AD. Therefore, TREM2 may be useful as an early peripheral biomarker for the development of AD.

Behaviour disorder caused by Cushing's syndrome in an older person.

An 81-year-old woman was hospitalised for behavioural disorders that had been progressively emerging over a period of few weeks. The symptoms appeared to worsen over time. A diagnosis of vascular dementia, complicated by psychosis, was initially hypothesised. The inefficacy of the antipsychotic/benzodiazepine medications used, along with the presence of hypertension, hypokalaemia and metabolic alkalosis (resistant to pharmacological attempts of correction), as well as the hirsutism and the development of several infections, led us to consider Cushing's syndrome. Endocrinological analysis suggested ectopic adrenocorticotropic hormone (ACTH) secretion. Although endogenous Cushing's syndrome is rare in older people, it should always be considered among the differential diagnosis of behavioural disorders.

Inhibition of cholinergic pathways in Drosophila melanogaster by α-conotoxins.

Nicotinic acetylcholine receptors (nAChRs) play a pivotal role in synaptic transmission of neuronal signaling pathways and are fundamentally involved in neuronal disorders, including Alzheimer's disease, Parkinson's disease, and schizophrenia. In vertebrates, cholinergic pathways can be selectively inhibited by α-conotoxins; we show that in the model organism Drosophila, the cholinergic component of the giant fiber system is inhibited by α-conotoxins MII, AuIB, BuIA, EI, PeIA, and ImI. The injection of 45 pmol/fly of each toxin dramatically decreases the response of the giant fiber to dorsal longitudinal muscle (GF-DLM) connection to 20 ± 13.9% for MII; 26 ± 13.7% for AuIB, 12 ± 9.9% for BuIA, 30 ± 11.3% for EI, 1 ± 1% for PeIA, and 34 ± 15.4% for ImI. Through bioassay-guided fractionation of the venom of Conus brunneus, we found BruIB, an α-conotoxin that inhibits Drosophila nicotinic receptors but not its vertebrate counterparts. GF-DLM responses decreased to 43.7 ± 8.02% on injection of 45 pmol/fly of BruIB. We manipulated the Dα7 nAChR to mimic the selectivity of its vertebrate counterpart by placing structurally guided point mutations in the conotoxin-binding site. This manipulation rendered vertebrate-like behavior in the Drosophila system, enhancing the suitability of Drosophila as an in vivo tool to carry out studies related to human neuronal diseases. .

Transforming conotoxins into cyclotides: Backbone cyclization of P-superfamily conotoxins.

Peptide backbone cyclization is a widely used approach to improve the activity and stability of small peptides but until recently it had not been applied to peptides with multiple disulfide bonds. Conotoxins are disulfide-rich conopeptides derived from the venoms of cone snails that have applications in drug design and development. However, because of their peptidic nature, they can suffer from poor bioavailability and poor stability in vivo. In this study two P-superfamily conotoxins, gm9a and bru9a, were backbone cyclized by joining the N- and C-termini with short peptide linkers using intramolecular native chemical ligation chemistry. The cyclized derivatives had conformations similar to the native peptides showing that backbone cyclization can be applied to three disulfide-bonded peptides with cystine knot motifs. Cyclic gm9a was more potent at high voltage-activated (HVA) calcium channels than its acyclic counterpart, highlighting the value of this approach in developing active and stable conotoxins containing cyclic cystine knot motifs.

E-learning to improve the drug prescribing in the hospitalized elderly patients: the ELICADHE feasibility pilot study.

BACKGROUND: E-learning is an efficient and cost-effective educational method. AIMS: This study aimed at evaluating the feasibility of an educational e-learning intervention, focused on teaching geriatric pharmacology and notions of comprehensive geriatric assessment, to improve drug prescribing to hospitalized elderly patients. METHODS: Eight geriatric and internal medicine wards were randomized to intervention (e-learning educational program) or control. Clinicians of the two groups had to complete a specific per group e-learning program in 30 days. Then, ten patients (aged ≥75 years) had to be consecutively enrolled collecting clinical data at hospital admission, discharge, and 3 months later. The quality of prescription was evaluated comparing the prevalence of potentially inappropriate medications through Beer's criteria and of potential drug-drug interactions through a specific computerized database. RESULTS: The study feasibility was confirmed by the high percentage (90 %) of clinicians who completed the e-learning program, the recruitment, and follow-up of all planned patients. The intervention was well accepted by all participating clinicians who judged positively (a mean score of >3 points on a scale of 5 points: 0 = useless; 5 = most useful) the specific contents, the methodology applied, the clinical relevance and utility of e-learning contents and tools for the evaluation of the appropriateness of drug prescribing. CONCLUSIONS: The pilot study met all the requested goals. The main study is currently ongoing and is planned to finish on July 2015.

Characterization of a novel peptide toxin from Acanthoscurria paulensis spider venom: a distinct cysteine assignment to the HWTX-II family.

Spider venom toxins have raised interest in prospecting new drugs and pesticides. Nevertheless, few studies are conducted with tarantula toxins, especially with species found in Brazil. This study aims to characterize chemically and biologically the first toxin isolated from Acanthoscurria paulensis venom. Ap1a consists of 48 amino acid residues and has a molecular mass of 5457.79 Da. The cloned gene encodes a putative sequence of 23 amino acid residues for the signal peptide and 27 for the pro-peptide. The sequence of the mature peptide is 60-84% identical with those of toxins of the HWTX-II family. Different from the structural pattern proposed for these toxins, the disulfide pairing of Ap1a is of the ICK type motif, which is also shared by the U1-TRTX-Bs1a toxin. Ap1a induced a dose-dependent and reversible paralytic effect in Spodoptera frugiperda caterpillars, with an ED50 of 13.0 ± 4.2 µg/g 8 h after injections. In the Drosophila melanogaster Giant Fiber circuit, Ap1a (1.14-22.82 µg/g) reduces both the amplitude and frequency of responses from GF-TTM and GF-DLM pathways, suggesting an action at the neuromuscular junction, which is mediated by glutamatergic receptors. It is also lethal to mice (1.67 µg/g, intracranial route), inducing effects similar to those reported with intracerebroventricular administration of NMDA. Ap1a (1 µM) does not alter the response induced by acetylcholine on the rhabdomyosarcoma cell preparation and shows no significant effects on hNav1.2, hNav1.4, hNav1.5, and hNav1.6 channels. Because of its unique sequence and cysteine assignment to the HWTX-II family, Ap1a is a significant contribution to the structure-function study of this family of toxins.

Association of rhinovirus and potentially pathogenic bacterial detections in the first 3 months of life with subsequent wheezing in childhood.

OBJECTIVE: Airway interactions between viruses, especially rhinoviruses, and potentially pathogenic bacteria (PPB; Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) in early infancy may increase the risk of subsequent wheezing and asthma. We evaluated the association between rhinovirus and PPB in the first 3 months of life and wheezing episodes before age 2 years and asthma at age 5-7 years. METHODS: An Australian community-based birth cohort of healthy children involved parents collecting nasal swabs weekly and completing symptom diaries daily until age 2 years. In a follow-up subset, asthma diagnosis was assessed annually until age 7 years. Swabs were analyzed by real-time polymerase chain reaction assays. Children were included if they returned symptom diaries beyond age 3 months (wheeze) or were reviewed at age 5-7 years (asthma). RESULTS: 1440 swabs were returned by 146 children in the first 3 months of life. Wheeze and asthma outcomes were recorded for 146 and 84 children, respectively. Each additional week of rhinovirus detection increased the incidence of wheezing before age 2 years by 1.16 times (95% confidence interval [CI]: 0.99-1.35). There were no significant associations between bacteria and wheeze. Each additional week with H. influenzae increased the odds of asthma at age 5-7 years by 135% (odds ratio: 2.35, 95% CI: 0.99-5.58). No significant interaction was observed between rhinovirus and PPB for wheezing or asthma. CONCLUSION: Early life rhinovirus infection was associated with wheezing before age 2 years and H. influenzae with asthma by age 5-7 years. Microbes may play an etiologic role in wheezing and asthma, warranting further study.

Prognosis of mucinous histology for patients with radically resected stage II and III colon cancer.

BACKGROUND: Previous studies investigating the prognostic role of mucinous histology of colorectal cancer produced conflicting results. This retrospective analysis was carried out in order to explore whether mucinous adenocarcinoma (MC) is associated with a comparatively worse prognosis than that of nonmucinous adenocarcinoma (NMC) for patients undergoing curative resection for stage II and III colon cancer. PATIENTS AND METHODS: This study involved 1025 unselected patients who underwent curative surgery for sporadic colon cancer and follow-up procedures at six different oncology departments. RESULTS: MCs accounted for 17.4% (n=178) of tumours. Patients with MC had 5- and 8-year overall survival rates of 78.6% and 68.8%, respectively, compared with 72.3% and 63.8%, respectively, for patients with nonmucinous tumours. Multivariate analysis using the Cox proportional hazards model showed that the clinically significant prognostic factors were stage of disease and adjuvant chemotherapy. No statistically significant interaction between mucinous histology and adjuvant chemotherapy was found. CONCLUSIONS: For patients with stage II and III colon cancer who underwent curative surgery, mucinous histology has no significant correlation with prognosis compared with NMC. This retrospective analysis suggests a comparable benefit from adjuvant chemotherapy for MC compared with NMC.

Pin1 contribution to Alzheimer's disease: transcriptional and epigenetic mechanisms in patients with late-onset Alzheimer's disease.

BACKGROUND: Neurofibrillary tangles and senile plaques are hallmarks of Alzheimer's disease (AD) although the molecular basis of their coexistence remains elusive. The peptidyl-prolyl cis/trans isomerase Pin1 acts on both tau and amyloid precursor protein to regulate their functions by influencing tau phosphorylation and amyloid precursor protein processing. OBJECTIVE: In order to identify potential biomarkers for AD in easily accessible cells and to gain insight into the relationship between the brain and peripheral compartments in AD pathology, we investigated Pin1 expression and activity in the peripheral blood mononuclear cells of subjects with late-onset AD (LOAD) and age-matched controls (CT). METHODS: Gene and protein expression, promoter methylation, Ser(16) phosphorylation and activity of Pin1 were evaluated in 32 samples from subjects with LOAD and in 28 samples from CT. RESULTS: In LOAD subjects, there was a statistically significant reduction in Ser(16) phosphorylation (-30%; p = 0.041) and promoter methylation (-8%; p = 0.001), whereas Pin1 expression was significantly increased (+74%; p = 0.018). CONCLUSION: The modifications of Pin1 found in LOAD subjects support its involvement in the pathogenesis of the disease with an important role being played by epigenetic mechanisms.

Interference between rhinovirus and other RNA respiratory viruses in the first 2-years of life: A longitudinal community-based birth cohort study.

BACKGROUND: Cross-sectional studies report negative associations between rhinovirus and other RNA respiratory viruses. However, longitudinal studies with frequent, serial sampling are needed to identify the directionality of this relationship and its nature. OBJECTIVE: To investigate the association between rhinovirus and other RNA respiratory viruses detected 1-week apart. METHODS: The Observational Research in Childhood Infectious Diseases cohort study was conducted in Brisbane, Australia (2010-2014). Parents collected nasal swabs weekly from birth until age 2-years. Swabs were analysed by real-time polymerase chain reaction. The association between new rhinovirus detections and five other RNA viruses (influenza, respiratory syncytial virus, parainfluenza viruses, seasonal human coronaviruses, and human metapneumovirus) in paired swabs 1-week apart were investigated. RESULTS: Overall, 157 children provided 8,101 swabs, from which 4,672 paired swabs 1-week apart were analysed. New rhinovirus detections were negatively associated with new pooled RNA respiratory virus detections 1-week later (adjusted odds ratio (aOR) 0.48; 95% confidence interval (CI): 0.13-0.83), as were pooled RNA virus detections with new rhinovirus detections the following week (aOR 0.34; 95%CI: 0.09-0.60). At the individual species level, rhinovirus had the strongest negative association with new seasonal human coronavirus detections in the subsequent week (aOR 0.34; 95%CI: 0.120.95) and respiratory syncytial virus had the strongest negative association with rhinovirus 1-week later (aOR 0.21; 95%CI: 0.050.88). CONCLUSION: A strong, negative bidirectional association was observed between rhinovirus and other RNA viruses in a longitudinal study of a community-based cohort of young Australian children. This suggests within-host interference between RNA respiratory viruses.

Role of the IGF/insulin system in longevity.

Human life expectancy is influenced by multiple determinants, including various environmental and genetic factors. Though the non-genetic factors are important, it is estimated that approximately 25-32% of the overall difference in human lifespan for survival after the age of 60 years depends on for by genetic polymorphisms among individuals. In addition, there are human homologues to many genes that affect lifespan in model organisms. In people, longevity genes might slow the rate of age-related changes in cells, increase resistance to environmental stresses like infection and injury, and reduce the risk of many age-related conditions. The best studied longevity pathway is probably the one involving insulin/IGF-1 signaling. The important role of IGF and insulin-related signaling pathways in the control of longevity of worms and insects is very well documented. In the mouse, several spontaneous or experimentally induced mutations that interfere with GH/IGF axis modulation lead to extended longevity. Increases in the average life span in these mutants range from approximately 20-70% depending on the nature of the endocrine defect, gender, diet, and/or genetic background. All the data in animals models and in the population studies support the evidence that this pathway drives an evolutionarily conserved network that regulates lifespan and affects longevity across species. Results obtained in humans are still controversial and further extensive studies are required to firmly establish a role of the IGF1 axis in modulation of human longevity. A better knowledge of the role of this pathway in humans may assist in the design of improved treatment methods for age-related diseases, delay the aging process and prolong the human lifespan.

Cord-blood respiratory syncytial virus antibodies and respiratory health in first 5 years of life.

OBJECTIVE: To determine the potential longer-term effects of maternal antenatal respiratory syncytial virus (RSV) vaccination, we examined the association between cord-blood RSV-neutralizing antibodies (RSV-NA) and RSV infections in the first 2 years of life, RSV-NA at 3 years, and respiratory health to age 5 years. METHODS: Two community-based Australian birth cohorts were combined. For children with at least one atopic parent, paired serum RSV-NA levels were compared in cord blood and at age 3 years. Weekly nasal swabs were collected in one cohort and during acute respiratory infections (ARI) in the other. Wheeze history up to age 5 years and physician-diagnosed asthma at 5 years was collected by parent report. RESULTS: In 264 children, each log10 increase of cord-blood RSV-NA level was associated with 37% decreased risk (adjusted incidence-rate-ratio [aIRR] 0.63; 95% confidence interval [CI]: 0.40-1.01) of RSV-ARI and 49% decreased risk (aIRR 0.51; 95% CI: 0.25-1.02) of RSV acute lower respiratory infections (ALRI) at 12-24 months of age. However, higher cord-blood RSV-NA was associated with increased risk of all-cause ALRI (aIRR 1.29; 95% CI: 0.99-1.69), wheeze-associated ALRI (aIRR 1.75; 95% CI: 1.08-2.82), and severe ALRI (aIRR 2.76; 95% CI: 1.63-4.70) at age 6-<12 months. Cord-blood RSV-NA was not associated with RSV-ARI in the first 6-months, RSV-NA levels at 3 years, or wheeze or asthma at 5 years. CONCLUSIONS: Higher levels of cord-blood RSV-NA did not protect against RSV infections during the first 6-months-of-life, time-to-first RSV-ARI, or wheeze or asthma in the first 5 years of life. Additional strategies to control RSV-related illness in childhood are needed.

Mucinous histology predicts for poor response rate and overall survival of patients with colorectal cancer and treated with first-line oxaliplatin- and/or irinotecan-based chemotherapy.

The objective of this study was to investigate the efficacy of first-line chemotherapy containing irinotecan and/or oxaliplatin in patients with advanced mucinous colorectal cancer. Prognostic factors associated with response rate and survival were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. The population included 255 patients, of whom 49 (19%) had mucinous and 206 (81%) had non-mucinous colorectal cancer. The overall response rates for mucinous and non-mucinous tumours were 18.4 (95% CI, 7.5-29.2%) and 49% (95% CI, 42.2-55.8%), respectively (P=0.0002). After a median follow-up of 45 months, median overall survival for the mucinous patients was 14.0 months compared with 23.4 months for the non-mucinous group (hazard ratio (HR), 1.74; CI 95%, 1.27-3.31; P=0.0034). After adjustment for significant features by multivariate Cox regression analysis, mucinous histology was associated with poor overall survival (HR, 1.593, 95% CI, 1.05-2.40; P=0.0267), together with performance status ECOG 2, number of metastatic sites > or =2, and peritoneal metastases. This retrospective analysis shows that patients with mucinous colorectal cancer have poor responsiveness to oxaliplatin/irinotecan-based first-line combination chemotherapy and an unfavourable prognosis compared with non-mucinous colorectal cancer patients.

Enamel and dentine of deciduous teeth Er:YAG laser prepared. A SEM study.

AIM: The aim of this study was to observe dentine and enamel surfaces of deciduous teeth under SEM after cavity preparation with Er:YAG laser using different fluences. The results showed that when using Er:YAG laser for cavity preparation in deciduous teeth, no carbonisation or cracks were observed on the enamel and dentine surfaces using energy output between 150-250 Mj, and frequency 15 Hz. The SEM images of the dentine and enamel surfaces were similar to previous studies on permanent teeth: enamel with a typical "lava flow" appearance as a result of an open core of the prism that has lost its typical hexagonal aspect and the dentine with opened tubules plus a difference in the mineral thickness between peritubular and intertubular. CONCLUSION: The difference between the SEM images of deciduous enamel and dentine when using three different energies (150-200-250 mJ) is not significant in order to recommend the use of one type of output energy. In addition, the SEM images are similar TO those of permanent teeth.

Apolipoprotein E gene in physiological and pathological aging.

INTRODUCTION: The genetic background plays a role on longevity. The distribution of the apolipoprotein E gene (APOE) variants (ε2, ε3, ε4) may differ across age groups, especially in the oldest old and despite geographical and ethnic specificities. Since the ε4 variant is associated with Alzheimer's disease (AD), it might represent an opportunity for exploring the relationship of APOE with physiological and pathological aging. AIM: To explore the role played by APOE genotype/alleles on physiological and pathological brain aging. MATERIALS AND METHODS: The study was conducted in a cohort of centenarians (n = 106), and two cohorts of octogenarians (without cognitive decline, n = 351 controls; and with AD, n = 294). RESULTS: No significant differences in genotype/allele distributions were observed comparing controls to centenarians. The prevalence of ε2/ε3, ε3/ε3, ε3/ε4 and ε4/ε4 genotypes were significantly different in centenarians compared to AD. The prevalence of ε2 and ε3 alleles were significantly higher in centenarians, whereas the ε4 was less frequent. The ε4 allele was positively associated with AD, whereas a negative association was found for ε2 and ε3 alleles. CONCLUSIONS: Our study indicates that ε4 allele is strongly associated with AD. APOE significantly affects AD risk, but apparently not longevity.