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

2nd Annual Faculty Research & Innovation Day Program

https://first.fanshawec.ca/cri_cripublications/1001/thumbnail.jp

2017 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1004/thumbnail.jp

2015 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1002/thumbnail.jp

2016 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1003/thumbnail.jp

Análisis de pertinencia de la implementación de una maestría en negocios internacionales en el Ecuador.

The purpose of this study is to highlight the importance of having highly trained professionals in the International Business area, due to the imminent globalization and increasing use of technology that has allowed access to international markets. Secondary research sources were used and it was found that Ecuador has a level of international trade with sufficient potential to match the regional average. Hence, it is necessary to forge human talent, able to understand the functioning of international markets and take advantage of commercial opportunities to meet the demands of contemporary society, consolidate the business sector, and boost productivity in order to achieve sustainable economic growth. In conclusion, the study of this discipline, helps professionals to link conceptions about the commercial reality of the country and provide timely solutions to face the challenges that arise at a national and international level.El propósito del presente estudio es destacar la importancia de contar con profesionales altamente capacitados en el área de Negocios Internacionales, debido a la inminente globalización y creciente uso de la tecnología que ha permitido el acceso a mercados internacionales. Se emplearon fuentes de investigación secundarias y se encontró que Ecuador tiene un nivel de comercio internacional con el suficiente potencial para equiparar la media regional. De ahí que, es necesario forjar talento humano, capaz de comprender el funcionamiento de los mercados internacionales y aprovechar las oportunidades comerciales para cumplir con las demandas de la sociedad contemporánea, consolidar el sector empresarial, e impulsar la productividad a fin de alcanzar el crecimiento económico sostenible. Se concluyó que el estudio de esta disciplina, ayuda a los profesionales a vincular concepciones sobre la realidad comercial del país y brindar soluciones oportunas para afrontar los retos que se presenten a nivel nacional e internacional

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

Genetic associations with age at dementia onset in the PSEN1 E280A Colombian kindred

INTRODUCTION: Genetic associations with Alzheimer's disease (AD) age at onset (AAO) could reveal genetic variants with therapeutic applications. We present a large Colombian kindred with autosomal dominant AD (ADAD) as a unique opportunity to discover AAO genetic associations. METHODS: A genetic association study was conducted to examine ADAD AAO in 340 individuals with the PSEN1 E280A mutation via TOPMed array imputation. Replication was assessed in two ADAD cohorts, one sporadic early-onset AD study and four late-onset AD studies. RESULTS: 13 variants had p<1x10(-7) or p<1x10(-5) with replication including three independent loci with candidate associations with clusterin including near CLU. Other suggestive associations were identified in or near HS3ST1, HSPG2, ACE, LRP1B, TSPAN10, and TSPAN14. DISCUSSION: Variants with suggestive associations with AAO were associated with biological processes including clusterin, heparin sulfate, and amyloid processing. The detection of these effects in the presence of a strong mutation for ADAD reinforces their potentially impactful role

Resilience to autosomal dominant Alzheimer’s disease in a Reelin-COLBOS heterozygous man

We characterized the world's second case with ascertained extreme resilience to autosomal dominant Alzheimer's disease (ADAD). Side-by-side comparisons of this male case and the previously reported female case with ADAD homozygote for the APOE3 Christchurch (APOECh) variant allowed us to discern common features. The male remained cognitively intact until 67 years of age despite carrying a PSEN1-E280A mutation. Like the APOECh carrier, he had extremely elevated amyloid plaque burden and limited entorhinal Tau tangle burden. He did not carry the APOECh variant but was heterozygous for a rare variant in RELN (H3447R, termed COLBOS after the Colombia-Boston biomarker research study), a ligand that like apolipoprotein E binds to the VLDLr and APOEr2 receptors. RELN-COLBOS is a gain-of-function variant showing stronger ability to activate its canonical protein target Dab1 and reduce human Tau phosphorylation in a knockin mouse. A genetic variant in a case protected from ADAD suggests a role for RELN signaling in resilience to dementia