58 research outputs found
Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.
We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease
Pooling/bootstrap-based GWAS (pbGWAS) identifies new loci modifying the age of onset in PSEN1 p.Glu280Ala Alzheimer\u27s disease
The literature on GWAS (genome-wide association studies) data suggests that very large sample sizes (for example, 50,000 cases and 50,000 controls) may be required to detect significant associations of genomic regions for complex disorders such as Alzheimer\u27s disease (AD). Because of the challenges of obtaining such large cohorts, we describe here a novel sequential strategy that combines pooling of DNA and bootstrapping (pbGWAS) in order to significantly increase the statistical power and exponentially reduce expenses. We applied this method to a very homogeneous sample of patients belonging to a unique and clinically well-characterized multigenerational pedigree with one of the most severe forms of early onset AD, carrying the PSEN1 p.Glu280Ala mutation (often referred to as E280A mutation), which originated as a consequence of a founder effect. In this cohort, we identified novel loci genome-wide significantly associated as modifiers of the age of onset of AD (CD44, rs187116, P=1.29 _ 10?12; NPHP1, rs10173717, P=1.74 _ 10?12; CADPS2, rs3757536, P=1.54 _ 10?10; GREM2, rs12129547, P=1.69 _ 10?13, among others) as well as other loci known to be associated with AD. Regions identified by pbGWAS were confirmed by subsequent individual genotyping. The pbGWAS methodology and the genes it targeted could provide important insights in determining the genetic causes of AD and other complex conditions
A quantitative analysis of complexity of human pathogen-specific CD4 T cell responses in healthy M. tuberculosis infected South Africans
Author Summary: Human pathogen-specific immune responses are tremendously complex and the techniques to study them ever expanding. There is an urgent need for a quantitative analysis and better understanding of pathogen-specific immune responses. Mycobacterium tuberculosis (Mtb) is one of the leading causes of mortality due to an infectious agent worldwide. Here, we were able to quantify the Mtb-specific response in healthy individuals with Mtb infection from South Africa. The response is highly diverse and 66 epitopes are required to capture 80% of the total reactivity. Our study also show that the majority of the identified epitopes are restricted by multiple HLA alleles. Thus, technical advances are required to capture and characterize the complete pathogen-specific response. This study demonstrates further that the approach combining identified epitopes into "megapools" allows capturing a large fraction of the total reactivity. This suggests that this technique is generally applicable to the characterization of immunity to other complex pathogens. Together, our data provide for the first time a quantitative analysis of the complex pathogen-specific T cell response and provide a new understanding of human infections in a natural infection setting
SUPLEMENTO DEL XV CONGRESO INTERNACIONAL DE ACTIVIDAD FÍSICA Y DEPORTE. 17,18 y 19 DE OCTUBRE DEL 2018. ENSENADA, BAJA CALIFORNIA, MÉXICO
Compendio, en formato artículo, de los mejores trabajos presentados en el XV CONGRESO INTERNACIONAL DE ACTIVIDAD FÍSICA Y DEPORTE celebrado los días 17,18 y 19 de octubre del 2018 en la Universidad Autónoma de Baja California en la ciudad de Ensenada, Baja California, México:La nutrición en la actividad física y deportiva: alimentos funcionales con nanotecnología, aplicaciones potenciales. González González, K.Y.; Huerta Plaza, B.A.; Amaya Parra, G. (118-130)Perfil antropométrico, físico y hábitos alimentarios en escolares indígenas de Tijuana México. Avendaño Cano, D.L.; Gómez Miranda, L.M.; Aburto Corona, J.A. (131-142)Relación entre el clima de aprendizaje en Educación Física y la percepción de los estudiantes en las competencias del profesorado. Baños, R; Ortiz-Camacho, M.M.; Baena-Extremera, A.; Granero-Gallegos, A.; Machado-Parra, J.P.; Rentería, I.; Acosta, I.; Ramírez, L. (143-153)Valoración de capacidades físicas, composición corporal y consumo de vitaminas en una competencia de Crossfit. Cervantes-Hernández, N.; Hernández Nájera, N.; Carrasco Legleu, C.E.; Candia Lujan, R.; Enríquez Del Castillo, L.A. (154-164)Relación de la actividad física, características antropométricas y VO2máx en jóvenes universitarios: características por género. Enríquez-del Castillo, L.A.; Cervantes-Hernández, N.; Carrasco-Legleu, C.E.; Candia Luján, R. (165-174)Entrenamiento vibratorio de cuerpo completo y sus efectos sobre la composición corporal en jóvenes universitarios. Flores-Chico, B.; Bañuelos-Teres, L.E.; Buendía Lozada, E.R.P. (175-183)Actualización curricular, plan 2016 de la Licenciatura en Cultura Física de la BUAP. Flores-Chico, B.; Flores-Flores, A.; López de La Rosa, LE.; Aguilar-Enríquez, R.I.; Caballero Gómez, JM; Villanueva-Huerta, JA. (184-192)Evaluación psicológica y de la musculatura isquiosural de basquetbolistas universitarias en distintas etapas deportivas. Moranchel-Charros, R.; Martínez-Velázquez, E.S. (193-203)Efecto del ejercicio físico sobre la fuerza, resistencia y riesgo de caída en mujeres adultas. Ortiz Ortiz, M; Espinoza Gutiérrez, R; Gómez Miranda, LM.; Guzmán Gutiérrez, EC.; Calleja Núñez, JJ. (204-212)Desigualdad vs igualdad numérica y su efecto en la técnica de jugadores de fútbol infantil. Vega-Orozco, SI; Gavotto Nogales, OI; Bernal Reyes, F; Horta Gim, MA; Sarabia Sainz, HM. (213-224
Regulatory nodD1 and nodD2 genes of Rhizobium tropici strain CIAT 899 and their roles in the early stages of molecular signaling and host-legume nodulation
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Effect of apolipoprotein genotype and educational attainment on cognitive function in autosomal dominant Alzheimers disease.
Autosomal dominant Alzheimers disease (ADAD) is genetically determined, but variability in age of symptom onset suggests additional factors may influence cognitive trajectories. Although apolipoprotein E (APOE) genotype and educational attainment both influence dementia onset in sporadic AD, evidence for these effects in ADAD is limited. To investigate the effects of APOE and educational attainment on age-related cognitive trajectories in ADAD, we analyzed data from 675 Presenilin-1 E280A mutation carriers and 594 non-carriers. Here we show that age-related cognitive decline is accelerated in ADAD mutation carriers who also have an APOE e4 allele compared to those who do not and delayed in mutation carriers who also have an APOE e2 allele compared to those who do not. Educational attainment is protective and moderates the effect of APOE on cognition. Despite ADAD mutation carriers being genetically determined to develop dementia, age-related cognitive decline may be influenced by other genetic and environmental factors
Effect of apolipoprotein genotype and educational attainment on cognitive function in autosomal dominant Alzheimer’s disease
Abstract Autosomal dominant Alzheimer’s disease (ADAD) is genetically determined, but variability in age of symptom onset suggests additional factors may influence cognitive trajectories. Although apolipoprotein E (APOE) genotype and educational attainment both influence dementia onset in sporadic AD, evidence for these effects in ADAD is limited. To investigate the effects of APOE and educational attainment on age-related cognitive trajectories in ADAD, we analyzed data from 675 Presenilin-1 E280A mutation carriers and 594 non-carriers. Here we show that age-related cognitive decline is accelerated in ADAD mutation carriers who also have an APOE e4 allele compared to those who do not and delayed in mutation carriers who also have an APOE e2 allele compared to those who do not. Educational attainment is protective and moderates the effect of APOE on cognition. Despite ADAD mutation carriers being genetically determined to develop dementia, age-related cognitive decline may be influenced by other genetic and environmental factors
PET evidence of preclinical cerebellar amyloid plaque deposition in autosomal dominant Alzheimer's disease-causing Presenilin-1 E280A mutation carriers
Background: In contrast to sporadic Alzheimer's disease, autosomal dominant Alzheimer's disease (ADAD) is associated with greater neuropathological evidence of cerebellar amyloid plaque (Aβ) deposition. In this study, we used positron emission tomography (PET) measurements of fibrillar Aβ burden to characterize the presence and age at onset of cerebellar Aβ deposition in cognitively unimpaired (CU) Presenilin-1 (PSEN1) E280A mutation carriers from the world's largest extended family with ADAD. Methods: 18F florbetapir and 11C Pittsburgh compound B (PiB) PET data from two independent studies – API ADAD Colombia Trial (NCT01998841) and Colombia-Boston (COLBOS) longitudinal biomarker study were included. The tracers were selected independently by the respective sponsors prior to the start of each study and used exclusively throughout. Template-based cerebellar Aβ-SUVR (standard-uptake value ratios) using a known-to-be-spared pons reference region (cerebellar SUVR_pons), to a) compare 28–56-year-old CU carriers and non-carriers; b) estimate the age at which cerebellar SUVR_pons began to differ significantly in carrier and non-carrier groups; and c) characterize in carriers associations with age, cortical SUVR_pons, delayed recall memory, and API ADAD composite score. Results: Florbetapir and PiB cerebellar SUVR_pons were significantly higher in carriers than non-carriers (p < 0.0001). Cerebellar SUVR_pons began to distinguish carriers from non-carriers at age 34, 10 years before the carriers’ estimated age at mild cognitive impairment onset. Florbetapir and PiB cerebellar SUVR_pons in carriers were positively correlated with age (r = 0.44 & 0.69, p < 0.001), cortical SUVR_pons (r = 0.55 & 0.69, p < 0.001), and negatively correlated with delayed recall memory (r = −0.21 & −0.50, p < 0.05, unadjusted for cortical SUVR_pons) and API ADAD composite (r = −0.25, p < 0.01, unadjusted for cortical SUVR_pons in florbetapir API ADAD cohort). Conclusion: This PET study provides evidence of cerebellar Aβ plaque deposition in CU carriers starting about a decade before the clinical onset of ADAD. Additional studies are needed to clarify the impact of using a cerebellar versus pons reference region on the power to detect and track ADAD changes, even in preclinical stages of this disorder. © 2021 The Author(s)Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
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