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1. APOE4 Increases Energy Metabolism in APOE-Isogenic iPSC-Derived Neurons

Author

Vanessa Budny, Yannic Knöpfli, Debora Meier, Kathrin Zürcher, Chantal Bodenmann, Siri L. Peter, Terry Müller, Marie Tardy, Cedric Cortijo, and Christian Tackenberg

Subjects
apolipoprotein E (APOE), Alzheimer’s disease, induced pluripotent stem cells (iPSCs), human neurons, energy metabolism, glycolysis, Cytology, QH573-671
Abstract

The apolipoprotein E4 (APOE4) allele represents the major genetic risk factor for Alzheimer’s disease (AD). In contrast, APOE2 is known to lower the AD risk, while APOE3 is defined as risk neutral. APOE plays a prominent role in the bioenergetic homeostasis of the brain, and early-stage metabolic changes have been detected in the brains of AD patients. Although APOE is primarily expressed by astrocytes in the brain, neurons have also been shown as source for APOE. However, the distinct roles of the three APOE isoforms in neuronal energy homeostasis remain poorly understood. In this study, we generated pure human neurons (iN cells) from APOE-isogenic induced pluripotent stem cells (iPSCs), expressing either APOE2, APOE3, APOE4, or carrying an APOE knockout (KO) to investigate APOE isoform-specific effects on neuronal energy metabolism. We showed that endogenously produced APOE4 enhanced mitochondrial ATP production in APOE-isogenic iN cells but not in the corresponding iPS cell line. This effect neither correlated with the expression levels of mitochondrial fission or fusion proteins nor with the intracellular or secreted levels of APOE, which were similar for APOE2, APOE3, and APOE4 iN cells. ATP production and basal respiration in APOE-KO iN cells strongly differed from APOE4 and more closely resembled APOE2 and APOE3 iN cells, indicating a gain-of-function mechanism of APOE4 rather than a loss-of-function. Taken together, our findings in APOE isogenic iN cells reveal an APOE genotype-dependent and neuron-specific regulation of oxidative energy metabolism.

Published
2024
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2. CULTURAL ADAPTATION AND RELIABILITY ANALYSIS OF THE EARLY CLINICAL ASSESSMENT OF BALANCE

Author

Ana Paula Bensemann Gontijo, Juliana Maria Pimenta Starling, Graziela Dulce Oliveira, Debora Meier, and Marisa Cotta Mancini

Subjects
Cerebral palsy, Postural balance, Child development, Validation studies, Pediatrics, RJ1-570
Abstract

ABSTRACT Objective: To translate the Early Clinical Assessment of Balance (ECAB), an assessment scale developed specifically for children and adolescents with cerebral palsy into Brazilian Portuguese, evaluate semantic, idiomatic, experiential and conceptual equivalences, and to examine the face validity and the reliability within and between examiners of the Brazilian version. Methods: The following steps were done: translation by two independent translators; synthesis of translations; back translation into English; analysis of back-translations by a multidisciplinary committee and the author of the test to develop the final version of the test; test application training; administration of the translated version of ECAB (videotaped) in 60 children and adolescents with cerebral palsy; intra and inter-examiner reliability assessment. Reability was assessed by intraclass correlation coefficient (CCI). Results: The discrepancies found were related mainly to semantic equivalence and, therefore, there was no need to make cultural adaptations in any of the 13 items on the scale. The rate of agreement was greater than 90% and the reliability of the ECAB-Portuguese total score was excellent both for the intra-rater test (CCI=1.00) and for the inter-rater test (CCI=0.998). Likewise, the reliability evaluation of each of the scale items was also excellent. Conclusions: The translated version of the ECAB into Portuguese provides a tool for the evaluation of the specific balance for children and adolescents with cerebral palsy with different levels of functioning.

Published
2019
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3. Adaptação cultural e análise da confiabilidade da early clinical assessment of balance

Author

Juliana Maria Pimenta Starling, Graziela Dulce Oliveira, Debora Meier, Ana Paula Bensemann Gontijo, and Marisa Cotta Mancini

Subjects
Male, 030506 rehabilitation, Intraclass correlation, Paralisia cerebral, Desenvolvimento infantil, Cerebral palsy, 03 medical and health sciences, 0302 clinical medicine, Brazilian Portuguese, Semantic equivalence, Estudos de validação, medicine, Humans, Equilíbrio postural, Child, Child development, Reliability (statistics), Face validity, Observer Variation, Cultural Characteristics, Cerebral Palsy, lcsh:RJ1-570, Infant, Reproducibility of Results, lcsh:Pediatrics, Original Articles, medicine.disease, language.human_language, Disabled Children, Test (assessment), Validation studies, Scale (social sciences), Child, Preschool, Health Care Surveys, Postural balance, Pediatrics, Perinatology and Child Health, language, Female, 0305 other medical science, Psychology, 030217 neurology & neurosurgery, Brazil, Clinical psychology
Abstract

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais Objective: To translate the Early Clinical Assessment of Balance (ECAB), an assessment scale developed specifically for children and adolescents with cerebral palsy into Brazilian Portuguese, evaluate semantic, idiomatic, experiential and conceptual equivalences, and to examine the face validity and the reliability within and between examiners of the Brazilian version. Methods: The following steps were done: translation by two independent translators; synthesis of translations; back translation into English; analysis of back-ranslations by a multidisciplinary committee and the author of the test to develop the final version of the test; test application training; administration of the translated version of ECAB (videotaped) in 60 children and adolescents with cerebral palsy; intra and inter-examiner reliability assessment. Reability was assessed by intraclass correlation coefficient (CCI). Results: The discrepancies found were related mainly to semantic equivalence and, therefore, there was no need to make cultural adaptations in any of the 13 items on the scale. The rate of agreement was greater than 90% and the reliability of the ECABPortuguese total score was excellent both for the intra-rater test (CCI=1.00) and for the inter-rater test (CCI=0.998). Likewise, the reliability evaluation of each of the scale items was also excellent. Conclusions: The translated version of the ECAB into Portuguese provides a tool for the evaluation of the specific balance for children and adolescents with cerebral palsy with different levels of functioning. Objetivo: Traduzir a Early Clinical Assessment of Balance (ECAB), escala de avaliação do equilíbrio desenvolvida especificamente para crianças e adolescentes com paralisia cerebral (PC) para a língua portuguesa do Brasil; avaliar as equivalências semânticas, idiomáticas, experiencial e conceituais; e examinar a validade de face e a confiabilidade intra e interavaliadores da versão brasileira. Métodos: Estudo envolveu tradução do instrumento por dois tradutores independentes; síntese das traduções; retrotradução para o inglês; análise das retrotraduções por um comitê multidisciplinar; treinamento; administração da versão traduzida da ECAB (gravadas em vídeo) em 60 crianças e adolescentes com PC; e avaliação da confiabilidade intra e interexaminadores. A confiabilidade foi avaliada por meio do coeficiente de correlação intraclasse (CCI). Resultados: As discrepâncias encontradas foram referentes principalmente à equivalência semântica e, portanto, não houve necessidade da realização de adaptações culturais em nenhum dos 13 itens da escala. A taxa de concordância foi maior que 90%, e a confiabilidade do escore total da ECAB-português foi excelente tanto para o teste intra-avaliador (CCI=1,00) quanto para interavaliadores (CCI=0,998). Da mesma forma, a avaliação da confiabilidade de cada um dos itens da escala também foi excelente. Conclusões: A versão traduzida da ECAB para o português disponibiliza, para os profissionais da reabilitação infantil, um instrumento confiável de avaliação do equilíbrio específico para crianças e adolescentes com PC com diferentes níveis de funcionalidade.

Published
2017

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