Department of Biochemistry, Institute of Biomedical Sciences, Dow University of Health Sciences, Karachi, Pakistan.
Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan.
Brain Res. 2021 May 1;1758:147342. doi: 10.1016/j.brainres.2021.147342. Epub 2021 Feb 4.
Treatment of Alzheimer's Disease (AD) remains an unsolved issue despite the pronounced global attention it has received from researchers over the last four decades. Determining the primary cause of the disease is challenging due to its long prodromal phase and multifactorial etiology. Regardless, academic disagreements amongst the scientific community have helped in making significant advancements in underpinning the molecular basis of disease pathogenesis. Substantial development in fluid and imaging biomarkers for AD led to a sharp turn in defining the disease as a molecular construct, dispensing its clinical definition. With conceptual progress, revisions in the diagnostic criteria of AD were made, culminating into the research framework proposed by National Institute on Aging and Alzheimer's Association in 2018 which unified different stages of the disease continuum, giving a common language of AT(N) classification to researchers. With realization that dementia is the final stage of AD spectrum, its early diagnosis by means of cerebrospinal fluid biomarkers, Positron Emission Tomography and Magnetic Resonance Imaging of the brain holds crucial importance in discovering ways of halting the disease progression. This article maps the insights into the pathogenesis as well as the diagnostic criteria and tests for AD as these have evolved over time. A contextualized timeline of how the understanding of AD has matured with advancing knowledge allows future research to be directed and unexplored avenues to be prioritized.
尽管过去四十年研究人员对阿尔茨海默病（AD）给予了极大关注，但该病的治疗仍然是一个悬而未决的问题。由于该病有很长的前驱期和多种病因，因此确定其主要病因具有挑战性。尽管如此，科学界内部的学术分歧还是有助于深入了解疾病发病机制的分子基础方面取得了重大进展。AD 的液体和成像生物标志物的大量发展，使得人们可以更准确地将该病定义为一种分子结构，从而改变了其临床定义。随着概念的进步，AD 的诊断标准也进行了修订，最终形成了 2018 年美国国家老龄化研究所和阿尔茨海默病协会提出的研究框架，该框架统一了疾病连续体的不同阶段，为研究人员提供了一种通用的 AT(N)分类语言。人们逐渐认识到痴呆是 AD 谱系的最后阶段，因此通过脑脊液生物标志物、正电子发射断层扫描和大脑磁共振成像来早期诊断痴呆症对于发现阻止疾病进展的方法具有至关重要的意义。本文阐述了随着时间的推移，AD 的发病机制、诊断标准和检测方法的相关见解。通过了解 AD 认识的发展过程，为未来的研究指明了方向，并确定了需要优先探索的未知领域。
