PREADAPT: Identification of personalized inflammatory profiles of aging and senescence which are modified specifically by risk factors of dementia

PREADAPT：识别衰老和衰老的个性化炎症特征，这些特征会根据痴呆症的危险因素进行专门修改

• 批准号: MR/T046171/1
• 负责人: Natalie Marchant
• 金额: $ 51.38万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT046171%2F1
• 关键词: PREADAPT; Identification; personalized; inflammatory; profiles

Age represents by far the largest risk factor for dementia, including Alzheimer's disease (AD) dementia. However, not every person will develop dementia during aging. This indicates that age-related processes may not inescapably lead to dementia. Understanding the fundamental processes that occur during aging will likely offer new options to prevent or postpone the development of dementia. One such key mechanism is cellular senescence in which cells normally stop diving and also release of a senescence-associated secretory phenotype (SASP) profile of mediators which causes chronic inflammation. Several of the molecules included in SASP have been detected in fluids which are in direct contact with the brain raising the hypothesis that senescence and SASP is also occurring in brain cells during aging. PREADAPT will build on the hypothesis that chronic inflammation affects the path towards cell death, particularly in the brain. We will measure and quantified levels of SASP mediators, and will use information collected from this measurement to predict future cognitive decline and dementia. The levels and changes of these molecules are also affected by different genetic and environmental factors, which we will also use to generate a personalized risk profile for progressing to dementia. Members of the PREADAPT team have already conducted preliminary work to define a set of molecules believed to be important in this process. We will use a large number of pre-existing samples collected from older adults, and will integrate information about these molecules with known biological markers of Alzheimer's disease, and comorbidities to generate combined risk profiles. To achieve these goals, PREADAPT has gathered a team of leading experts in the field of neuroinflammation, epidemiology, genetics, epidemiological genetics, neuropsychology, and clinical research. The PREADAPT team has access to state-of-the-art methodology and to large studies where participants were observed over time, and studies that involved an intervention. A substantial amount of information was collected during these studies, which include brain imaging, genetic and other biological details. This unique configuration will enable PREADAPT to identify, before someone develops dementia, age-related profiles to inform their personalized future risk of progressing to dementia. PREADAPT will also provide the first evidence showing whether this personalized risk profile is altered by specific interventions by including several intervention cohorts.

到目前为止，年龄是痴呆症的最大风险因素，包括阿尔茨海默病（AD）痴呆症。然而，并不是每个人都会在衰老过程中患上痴呆症。这表明与年龄有关的过程可能不可避免地导致痴呆症。了解衰老过程中发生的基本过程可能会为预防或推迟痴呆症的发展提供新的选择。一种这样的关键机制是细胞衰老，其中细胞通常停止潜水，并且还释放引起慢性炎症的介质的衰老相关分泌表型（SASP）谱。在与大脑直接接触的液体中检测到了SASP中包含的几种分子，这提出了衰老和SASP也发生在衰老过程中的脑细胞中的假设。PREADAPT将建立在慢性炎症影响细胞死亡途径的假设基础上，特别是在大脑中。我们将测量和量化SASP介质的水平，并将使用从该测量中收集的信息来预测未来的认知能力下降和痴呆。这些分子的水平和变化也受到不同遗传和环境因素的影响，我们还将利用这些因素来生成进展为痴呆症的个性化风险特征。PREADAPT小组的成员已经进行了初步工作，以确定一组被认为在这一过程中很重要的分子。我们将使用从老年人收集的大量预先存在的样本，并将这些分子的信息与阿尔茨海默病的已知生物标志物和合并症相结合，以生成综合风险特征。为了实现这些目标，PREADAPT聚集了神经炎症，流行病学，遗传学，流行病学遗传学，神经心理学和临床研究领域的领先专家团队。PREADAPT团队可以使用最先进的方法和大型研究，其中对参与者进行了长期观察，以及涉及干预的研究。在这些研究中收集了大量的信息，包括大脑成像，遗传和其他生物学细节。这种独特的配置将使PREADAPT能够在某人患上痴呆症之前识别与年龄相关的特征，以告知他们个性化的未来进展为痴呆症的风险。PREADAPT还将通过纳入多个干预队列，提供第一个证据，表明这种个性化风险特征是否会因特定干预而改变。