Presymptomatic Diagnosis and Gene Therapy for Alzheimer’s Disease: Genomic, Therapeutic, and Ethical Aspects—A Systematic Review

Over the past three decades, genomic and epigenetic sciences have identified more than 70 genes involved in the molecular pathophysiology of Alzheimer’s disease (AD). DNA methylation, abnormal histone and chromatin regulation and the action of various miRNAs induce AD. The identification of mutated genes has paved the way for the development of diagnostic kits and the initiation of gene therapy trials. However, despite major advances in neuroscience research, there is yet no suitable treatment for AD. Therefore, the early diagnosis of this neurodegenerative disease raises several ethical questions, including the balance between the principle of non-maleficence and the principle of beneficence. The aims of this research were to present the genomic and ethical aspects of AD, and to highlight the ethical principles involved in its presymptomatic diagnosis and therapy. A systematic review of the literature in PubMed, Google Scholar and Science Direct was carried out to outline the genomic aspects and ethical principles relating not only to the presymptomatic diagnosis of AD, but also to its gene therapy. A total of 16 publications were selected. AD is a multifactorial disease that can be genetically classified into Sporadic Alzheimer’s Disease and Familial Alzheimer’s Disease based on family history. Gene therapy targeting specific disease-causing genes is a promising therapeutic strategy. Advancements in artificial intelligence applications may enable the prediction of AD onset several years in advance. While early diagnosis of AD may empower patients with full decision competence for early decision-making, it also carries implications for the patient’s family members, who are at risk of developing the disease, potentially becoming a source of confusion or anxiety. AD has a significant impact on the life of individuals at risk and their families. Given the absence of disease modifying therapy, genetic screening and early diagnosis for this condition raise ethical issues that must be carefully considered in the context of fundamental bioethical principles, including autonomy, beneficence, non-maleficence, and justice.

指纹光谱特征揭示叶斑病时空动态发展以实现显症前诊断

植物病原菌不断危害农业生产和粮食安全。因此,病害发展早期的动态表征对病变监测和显症前诊断至关重要。高光谱成像(HSI)在跟踪病害初始侵染部位的动态进程以进行显症前诊断方面具有巨大潜力。然而,目前尚无相关文献提取出早期感染阶段活体叶片病变组织的指纹光谱特征(FSS),也没有探究HSI的检测机制。其中FSS是指能够表征特定植物病害的独特、有代表性的光谱特征。在本研究中,基于时序HSI数据分析,提取了接种Bipolaris sorokiniana的大麦叶片的FSS,以表征叶斑病症状发展,实现显症前诊断。还研究了叶斑病早期发展阶段叶片的光谱和生化响应。本文所提取的全波段FSS能够捕捉病变发展过程中褪绿组织和坏死组织的独特特征,从而原位可视化植物-病原菌像素级的早期互作动态进程。进一步,实现了接种后24 h叶斑病的显症前诊断,比传统的聚合酶链反应(PCR)测定或生化测定提前了12 h。为了揭示HSI显症前诊断的机制,还建立了叶片的平均光谱响应与其生化指标(叶绿素、类胡萝卜素、丙二醛、抗坏血酸和还原型谷胱甘肽)之间的定量关系,回归模型在预测集上的Rp2均高于0.84。总体结果表明,HSI反映了活体植物特性的变化,所提取的FSS可成功跟踪叶斑病发生发展的时空动态进程,实现显症前诊断。在其他植物病害上的试验表明,该方法在植物病害早期控制方面具有较大的推广潜力。