Abstract
Leukoaraiosis (LA), also called white matter lesions (WMLs) and white matter hyperintensities (WMHs), is a frequent neuroimaging finding commonly seen on magnetic resonance imaging brain scans of elderly people with prevalence ranging from 50% to 100%. Although it remains asymptomatic, LA is not considered to be benign, and it is showed to be related to a host of poor clinical outcomes and increases the risk of disability, dementia, depression, stroke, and the overall morbidity and mortality. Pathologically, LA is characterized by loss of myelin and axons, patchy demyelination, and denudation of ependyma in regions of WMH. Age and hypertension are the most importantly established risk factors for LA. However, the precise pathogenic mechanisms remain unclear. Together with the previous findings, our recent genetic results strongly supported that LA is associated with immune response and neuroinflammation. Therefore, we confidently hypothesized that LA was not only a common neuroimaging phenomenon in the elderly but also an emerging neuroinflammatory disorder in the central nervous system. This article focusing on neuroimaging classification, genetics basis, and putative molecular mechanism introduced the basic knowledge and current status of LA and put forward some of our research ideas and results from our molecular genetics research, which may pave the way for deciphering the putative pathogenic mechanism, risk factor, epigenetic index, and its application in diagnostic agents or drug target for prevention and treatment. Thus, it could provide clinicians and researchers with a specific and modern overview of LA to enable the understanding of recent progress and future directions in this illness.
About the authors
Qing Lin obtained her Bachelor of Medicine degree from the Fujian Medical University in 1994. After that, she worked as a house physician in the Department of Neurology, The First Affiliated Hospital of Xiamen University until 2005. She received her Master’s of Medicine degree from Fujian Medical University in 2008, where her research interest lies in the neurodegenerative and cerebrovascular diseases. In 2009, she attended the Institute for Biomedical Research, Xiamen University, to pursue a PhD, where her research focused on translational medicine. With 20 years of working experience on brain disorders, Dr. Lin is outstanding in the diagnosis and treatment of geriatrics (Parkinson’s diseases and dementia), cerebrovascular disorders (Wilson’s disease, cerebral cavernous malformations, identifying idiopathic normal pressure hydrocephalus, and cerebral amyloid angiopathy), neuroimmune disorders (myasthenia gravis and neuromyelitis optica), and neural infection diseases.
Wen-Qing Huang received his Bachelor of Science degree in Biology Engineering in 2010 from South-Center University for Nationalities, Wuhan, Hubei, China. He subsequently joined Dr. Chi-Meng Tzeng’s laboratory at the Institute for Biomedical Research, Xiamen University, to pursue graduate study, where he worked on a pharmacogenomic study of the phosphodiesterase type 5 inhibitors and azathioprine treatment for erectile dysfunction and myasthenia gravis, respectively, and personalized theranostics for Wilson’s disease and cerebral cavernous malformations as well as gastric cancer, collaborating with The First Affiliated Hospital of Xiamen University. Since 2012, he is a PhD student in Dr. Chi-Meng Tzeng’s laboratory at the School of Pharmaceutical Sciences. His research focuses on deciphering the molecular mechanism of CNS neuroinflammatory disorders, such as leukoaraiosis and neuromyelitis optica.
Chi-Meng Tzeng received comprehensive graduate training in Tsinhua University (Radiation Biology, advised by Dr. Rong-Long Pan) and Stanford University (Medical School in Biochemistry, advised by Dr. Arthur Kornberg) in the 1990s. Moreover, he also worked extensively in both academic and industrial executive positions at Academic Sinica, Institute of BioAgricultural Science, National Taiwan University Hospital, Department of Biomedical Research, U-Vision Biotech, VitaGenomics, GeneCore, MaxyBio, and Beckman Coulter since 2000. Dr. Tzeng is presently the professor and executive director of the Center of Translational Medicine Research, Institute for Biomedical Research and College of Pharmacy, Xiamen University. Recently, he is leading clinical resources, academic force, and bioindustrial energy to decipher the biomarkers, molecular mechanism, and personalized theranostics in projects of adenocarcinoma (EGFR signaling pathways), leukemia (A-/C-ML fusion genes), and leukoaraiosis (genetic diagnosis or prognosis). His laboratory is also committed to finding a systematic genomic approach, from the mesenchymal stem cells to committed cells, for new drug applications.
Acknowledgments
This study was approved by the Xiamen Ethical Committee and supported by the Fujian Provincial Science and Technology (grant no. 2012Y0064), the Xiamen Science and Technology Bureau (grant no. 350Z20121153), and the National Natural Science Foundation of China (grant nos. 81272445 and 81101331).
Conflicts of interest statement: The authors state that there are no conflicts of interest in this study.
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