PDF(Pubmed)
Abstract：
UNASSIGNED: Our limited understanding of the mechanisms that trigger the emergence of Alzheimer\'s disease (AD) has contributed to the lack of interventions that stop, prevent, or fully treat this disease. We believe that the development of a non-human primate model of AD will be an essential step toward overcoming limitations of other model systems and is crucial for investigating primate-specific mechanisms underlying the cellular and molecular root causes of the pathogenesis and progression of AD.
UNASSIGNED: A new consortium has been established with funding support from the National Institute on Aging aimed at the generation, characterization, and validation of Marmosets As Research Models of AD (MARMO-AD). This consortium will study gene-edited marmoset models carrying genetic risk for AD and wild-type genetically diverse aging marmosets from birth throughout their lifespan, using non-invasive longitudinal assessments. These include characterizing the genetic, molecular, functional, behavioral, cognitive, and pathological features of aging and AD.
UNASSIGNED: The consortium successfully generated viable founders carrying PSEN1 mutations in C410Y and A426P using CRISPR/Cas9 approaches, with germline transmission demonstrated in the C410Y line. Longitudinal characterization of these models, their germline offspring, and normal aging outbred marmosets is ongoing. All data and resources from this consortium will be shared with the greater AD research community.
UNASSIGNED: By establishing marmoset models of AD, we will be able to investigate primate-specific cellular and molecular root causes that underlie the pathogenesis and progression of AD, overcome limitations of other model organisms, and support future translational studies to accelerate the pace of bringing therapies to patients.
UNASSIGNED: A new consortium has been established with funding support from the National Institute on Aging aimed at the generation, characterization, and validation of Marmosets As Research Models of AD (MARMO-AD). This consortium will study gene-edited marmoset models carrying genetic risk for AD and wild-type genetically diverse aging marmosets from birth throughout their lifespan, using non-invasive longitudinal assessments. These include characterizing the genetic, molecular, functional, behavioral, cognitive, and pathological features of aging and AD.
UNASSIGNED: The consortium successfully generated viable founders carrying PSEN1 mutations in C410Y and A426P using CRISPR/Cas9 approaches, with germline transmission demonstrated in the C410Y line. Longitudinal characterization of these models, their germline offspring, and normal aging outbred marmosets is ongoing. All data and resources from this consortium will be shared with the greater AD research community.
UNASSIGNED: By establishing marmoset models of AD, we will be able to investigate primate-specific cellular and molecular root causes that underlie the pathogenesis and progression of AD, overcome limitations of other model organisms, and support future translational studies to accelerate the pace of bringing therapies to patients.
摘要：
■我们对引发阿尔茨海默病（AD）出现的机制的了解有限，这导致了缺乏阻止，防止，或完全治疗这种疾病。我们认为，开发非人类灵长类动物模型将是克服其他模型系统局限性的重要一步，对于研究灵长类动物特异性机制是AD发病机理和进展的细胞和分子根本原因至关重要。
■在国家老龄研究所的资助下，建立了一个新的财团，表征，并验证了Marmosets作为AD研究模型(MARMO-AD)。该联盟将研究基因编辑的猿猴模型，这些模型具有AD的遗传风险，并且在整个生命周期中从出生起就具有野生型遗传多样性的衰老猿猴，使用非侵入性纵向评估。这些包括表征遗传，分子，功能，行为，认知，衰老和AD的病理特征。
■该联盟使用CRISPR/Cas9方法成功地在C410Y和A426P中产生了携带PSEN1突变的可行创始人，在C410Y系中表现出种系传播。这些模型的纵向特征，它们的种系后代，正常的老化近交的猕猴桃正在进行中。该联盟的所有数据和资源将与更大的AD研究社区共享。
■通过建立AD的Marmoset模型，我们将能够研究作为AD发病机制和进展基础的灵长类动物特异性细胞和分子根本原因，克服了其他模式生物的局限性，并支持未来的转化研究，以加快为患者带来治疗的步伐。
■在国家老龄研究所的资助下，建立了一个新的财团，表征，并验证了Marmosets作为AD研究模型(MARMO-AD)。该联盟将研究基因编辑的猿猴模型，这些模型具有AD的遗传风险，并且在整个生命周期中从出生起就具有野生型遗传多样性的衰老猿猴，使用非侵入性纵向评估。这些包括表征遗传，分子，功能，行为，认知，衰老和AD的病理特征。
■该联盟使用CRISPR/Cas9方法成功地在C410Y和A426P中产生了携带PSEN1突变的可行创始人，在C410Y系中表现出种系传播。这些模型的纵向特征，它们的种系后代，正常的老化近交的猕猴桃正在进行中。该联盟的所有数据和资源将与更大的AD研究社区共享。
■通过建立AD的Marmoset模型，我们将能够研究作为AD发病机制和进展基础的灵长类动物特异性细胞和分子根本原因，克服了其他模式生物的局限性，并支持未来的转化研究，以加快为患者带来治疗的步伐。
