Alzheimers Disease Apolipoprotein Pathology for Treatment Elucidation and Develo...
Alzheimers Disease Apolipoprotein Pathology for Treatment Elucidation and Development Sofia ref. 115975
APOEɛ4 has long been known as a risk factor of LOAD, yet the biological mechanisms through which it acts remain largely unknown and affect both the vasculature and the brain. This complexity and pleiotropic influence demands an in...
APOEɛ4 has long been known as a risk factor of LOAD, yet the biological mechanisms through which it acts remain largely unknown and affect both the vasculature and the brain. This complexity and pleiotropic influence demands an integrated hypothesis-free approach to embark on a fundamental study of the gene, the phenotype and modulation by other risk factors. ADAPTED proposes to leverage extreme genotypes from consortium cohorts dating back more than 25 years to generate, and use existing, lines of human induced pluripotent stem cells (iPSC). These cells, with blood cells, will form the backbone of the research programme. We will differentiate them to the most relevant cells for APOE and AD studies and with gene editing create bespoke homozygote ɛ3 and ɛ2 cells for a highly focussed effort on APOE biology. A series of experiments including neuron-astrocyte and macrophage-endothelium co-culture and Organ on a Chip models combined with state-of-the-art omics including quantitative proteomics assays will generate data for rigorous integrated analysis to uncover new signalling pathways related to APOE. Lipid homeostasis, endocytosis, metabolism and immune systems pathways will be investigated in a broad approach. The findings are expected to lead to identification of new treatment approaches and blood based AD signatures with a temporal dimension from the earliest stages of risk identification and progression through MCI to AD. Testing and validation of biomarkers will be performed by examining their influence and predictive capacity in a longitudinal ADAPTED cohort harmonised using a combination of approaches for marker and diagnostic consistency. The impact of this work can be expected to include seminal new finding to illuminate the research path towards new diagnostics and therapies to attenuate the rising tide of suffering from AD. The vision is a follow on with clinical proof of concept validating utility of the results within two years of the end of ADAPTED.ver más
Seleccionando "Aceptar todas las cookies" acepta el uso de cookies para ayudarnos a brindarle una mejor experiencia de usuario y para analizar el uso del sitio web. Al hacer clic en "Ajustar tus preferencias" puede elegir qué cookies permitir. Solo las cookies esenciales son necesarias para el correcto funcionamiento de nuestro sitio web y no se pueden rechazar.
Cookie settings
Nuestro sitio web almacena cuatro tipos de cookies. En cualquier momento puede elegir qué cookies acepta y cuáles rechaza. Puede obtener más información sobre qué son las cookies y qué tipos de cookies almacenamos en nuestra Política de cookies.
Son necesarias por razones técnicas. Sin ellas, este sitio web podría no funcionar correctamente.
Son necesarias para una funcionalidad específica en el sitio web. Sin ellos, algunas características pueden estar deshabilitadas.
Nos permite analizar el uso del sitio web y mejorar la experiencia del visitante.
Nos permite personalizar su experiencia y enviarle contenido y ofertas relevantes, en este sitio web y en otros sitios web.