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

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，与年龄相关的过程可能不会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。其中一个关键机制是细胞衰老，细胞通常停止潜水，并释放与衰老相关的分泌表型(SASP)，这会导致慢性炎症。在与大脑直接接触的液体中发现了SASP中的几个分子，这提出了衰老和SASP也在衰老过程中发生在脑细胞中的假设。PREADAPT将建立在一个假设的基础上，即慢性炎症影响细胞死亡的途径，特别是在大脑中。我们将测量和量化SASP介体的水平，并将使用从这种测量中收集的信息来预测未来的认知衰退和痴呆症。这些分子的水平和变化也受到不同的遗传和环境因素的影响，我们也将利用这些因素来生成进展为痴呆症的个性化风险概况。PREADAPT团队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至关重要的分子。我们将使用从老年人那里收集的大量预先存在的样本，并将有关这些分子的信息与阿尔茨海默病的已知生物标记物和共病相结合，以生成综合的风险概况。为了实现这些目标，PREADAPT聚集了一支由神经炎症、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组成的团队。PREADAPT团队可以获得最先进的方法学，可以获得长期观察参与者的大型研究，以及涉及干预的研究。在这些研究过程中收集了大量信息，包括大脑成像、遗传和其他生物学细节。这一独特的配置将使PREADAPT能够在某人患上痴呆症之前识别与年龄有关的简档，以告知他们个性化的未来进展为痴呆症的风险。PREADAPT还将提供第一个证据，表明这种个性化的风险概况是否因包括几个干预队列而被特定干预措施改变。

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.