Identification of biomarkers associated with Alzheimer’s disease progression that correlate with responses to medications.

Alzheimer’s disease (AD) manifests with strikingly different ages and sites of onset, progresses at different rates and in different anatomic directions, and has varied responses to treatment 1. Disease-modifying AD clinical trials have been disappointing; however, detailed analyses often show a subset of patients with improved outcomes 2–5. We hypothesize that AD is heterogeneous and only subsets of patients may respond to each treatment. Using computational analysis, we propose to identify biomarkers that correlate with the four critical clinical variables (age and site of onset, rate and direction of progression) and to test whether those markers correlate with responses to AD medications. The results of our analysis could provide unparalleled insights into whether a subject would respond, or not, to an investigational medication and whether a subject is likely to have rapid disease progression. It could also inform the basis of inclusion criteria for future clinical trials, ultimately increasing the likelihood of a positive outcome for both the investigational medication and the research subjects.

阿尔茨海默病（Alzheimer’s Disease, AD）的发病年龄与发病部位差异显著，疾病进展速度、解剖学进展方向各不相同，且对治疗的应答情况存在明显异质性¹。针对AD的疾病修饰疗法临床试验大多未能达到预期终点，但细致的亚组分析常可发现一小部分患者的临床结局得到改善²⁻⁵。本研究假设AD具有显著异质性，仅特定患者亚组可对某一治疗方案产生应答。本研究拟通过计算分析，识别与四大核心临床变量（发病年龄、发病部位、疾病进展速度及进展方向）相关的生物标志物（biomarker），并验证这些标志物是否与AD治疗药物的应答情况存在关联。本分析的结果可提供无可比拟的精准预判依据，帮助判断受试者对试验性药物的应答情况，以及受试者是否存在疾病快速进展的风险。该研究结果还可为未来临床试验的纳入标准制定提供依据，最终提升试验性药物与研究受试者双方获得阳性试验结果的可能性。