Investigating the Neurodevelopmental and Neurodegenerative Pathology of Down syndrome to Identify Neurophysiological Biomarkers in Patients with Alzheimer's disease: a Narrative Review Study
Investigating the Neurodevelopmental and Neurodegenerative Pathology of Down syndrome to Identify Neurophysiological Biomarkers in Patients with Alzheimer's disease: a Narrative Review Study
Fatemeh Safaei,1,*Dariush D. Farhud,2Ali Ahmadi,3
1. B.Sc. Student, Department of Psychology, Faculty of Humanities, Islamic Azad University Sari Branch, Sari, Iran 2. Professor, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran 3. M.Sc. Student, Department of Genetics, Faculty of Advanced Technologies and Science in Medicine, Islamic Azad University Tehran Medical Branch, Tehran, Iran
Introduction: The human brain is a complex organ composed of well-organized parts that work together to control body functions and regulate the higher functions of the mind that make us human. The growth of the human brain begins as a neural groove from a specific part of the ectoderm, the neuroectoderm, and forms the neural tube after the end of the third week of pregnancy. Primary and secondary brain vesicles through the progressive production of neural tissue from the neural tube around 4 and 5 weeks of gestation, respectively. The ventricles of the brain produce cerebrospinal fluid, which regulates the homeostasis of the interstitial fluid of the brain and acts as a hydromechanical protector of the central nervous system. People with Down syndrome (DS) suffer from developmental delay, mental retardation, and early onset of neurodegeneration, Alzheimer-like disease, or early-onset dementia caused by an extra chromosome 21. Studying the changes at the anatomical, cellular, and molecular levels involved may help to understand the pathogenesis and develop targeted therapies, not only medical, but also surgical, cell therapy, and gene therapy, etc., for people with DS. Cross-frequency coupling (CFC) mechanisms play a central role in brain activity. The pathophysiological mechanisms underlying many brain disorders, such as Alzheimer's disease (AD), may produce unique patterns of brain activity detectable by electroencephalography (EEG). Identifying biomarkers for the diagnosis of AD is also an ambition among research teams working in Down syndrome (DS), given the increased susceptibility of individuals with DS to develop early-onset AD (DS-AD). We aim to identify key developmental manifestations. Neuroscience, finding knowledge gaps, and trying to build molecular networks to better understand mechanisms and clinical significance.
Methods: This study is a descriptive study with a Narrative Review approach in 2023 by searching for keywords such as: Neurodevelopmental, Neurodegenerative, Pathology, Neurophysiological, Biomarkers Alzheimer in reliable databases such as: Scopus, Elsevier, PubMed , Web of Science was done. Finally, 15 articles were found, of which 10 were included in the study.
Results: According to the studies from the articles, the results obtained are that, theta-gamma phase amplitude coupling (PAC) may be one of the first signs of EEG AD, and therefore may be used as an auxiliary tool for the diagnosis of cognitive decline in DS-AD works. We suggest that this field of research could potentially provide clues to the biophysical mechanisms underlying cognitive dysfunction in DS-AD and create opportunities to identify EEG-based biomarkers with diagnostic and prognostic utility in DS-AD. Despite growing preclinical and clinical evidence supporting the use of EEG to investigate the effects of AD pathology on neurophysiological parameters, currently applied diagnostic criteria still do not support the use of EEG-based biomarkers in AD clinical practice. A similar scenario has been observed in the field of research aimed at identifying biomarkers for AD in DS. For example, the protocol of the most ambitious AD biomarker initiative to date in adults with DS, the Alzheimer's Down Syndrome Consortium Biomarker Syndrome (ABC-DS), includes advanced measures of MRI but not EEG as outcome measures of functional connectivity. In this perspective, we rationalize the pursuit of PAC as a potential auxiliary tool in the study of pathophysiological processes underlying brain dynamics in DS-AD, as well as in the identification of EEG-based biomarkers with potential diagnostic and prognostic tools in DS-AD. From a basic science perspective, continued investigation of neural network dynamics in mouse models of DS may help to increase our understanding of how AD pathology evolves in individuals with DS, as well as to expand knowledge of the early neurophysiological symptoms of DS-AD. It could potentially be of clinical use. From the perspective of clinical practice, the development of non-invasive, low-cost and easily accessible biomarkers (such as EEG-based ones) for the diagnosis of AD may be an important step towards identifying individuals in the pre-clinical or pre-dromal stage. This disease, especially in the most susceptible populations as the case of DS.
Conclusion: Understanding the changes and developing characteristics of Down syndrome will help target therapy to improve clinical outcomes. Early targeted intervention/treatment for DS-related manifestations in the prenatal or postnatal period may be beneficial to rescue neuropathology and neurodegeneration in DS.