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      The Genetics of Alzheimer’s Disease in the Chinese Population

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          Abstract

          Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment. In China, the number of AD patients is growing rapidly, which poses a considerable burden on society and families. In recent years, through the advancement of genome-wide association studies, second-generation gene sequencing technology, and their application in AD genetic research, more genetic loci associated with the risk for AD have been discovered, including KCNJ15, TREM2, and GCH1, which provides new ideas for the etiology and treatment of AD. This review summarizes three early-onset AD causative genes ( APP, PSEN1, and PSEN2) and some late-onset AD susceptibility genes and their mutation sites newly discovered in China, and briefly introduces the potential mechanisms of these genetic susceptibilities in the pathogenesis of AD, which would help in understanding the genetic mechanisms underlying this devastating disease.

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          Most cited references98

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          Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database.

          The past decade has witnessed hundreds of reports declaring or refuting genetic association with putative Alzheimer disease susceptibility genes. This wealth of information has become increasingly difficult to follow, much less interpret. We have created a publicly available, continuously updated database that comprehensively catalogs all genetic association studies in the field of Alzheimer disease (http://www.alzgene.org). We performed systematic meta-analyses for each polymorphism with available genotype data in at least three case-control samples. In addition to identifying the epsilon4 allele of APOE and related effects, we pinpointed over a dozen potential Alzheimer disease susceptibility genes (ACE, CHRNB2, CST3, ESR1, GAPDHS, IDE, MTHFR, NCSTN, PRNP, PSEN1, TF, TFAM and TNF) with statistically significant allelic summary odds ratios (ranging from 1.11-1.38 for risk alleles and 0.92-0.67 for protective alleles). Our database provides a powerful tool for deciphering the genetics of Alzheimer disease, and it serves as a potential model for tracking the most viable gene candidates in other genetically complex diseases.
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            The role of apolipoprotein E in Alzheimer's disease.

            The epsilon4 allele of apolipoprotein E (APOE) is the major genetic risk factor for Alzheimer's disease (AD). Although there have been numerous studies attempting to elucidate the underlying mechanism for this increased risk, how apoE4 influences AD onset and progression has yet to be proven. However, prevailing evidence suggests that the differential effects of apoE isoforms on Abeta aggregation and clearance play the major role in AD pathogenesis. Other potential mechanisms, such as the differential modulation of neurotoxicity and tau phosphorylation by apoE isoforms as well as its role in synaptic plasticity and neuroinflammation, have not been ruled out. Inconsistent results among studies have made it difficult to define whether the APOE epsilon4 allele represents a gain of toxic function, a loss of neuroprotective function, or both. Therapeutic strategies based on apoE propose to reduce the toxic effects of apoE4 or to restore the physiological, protective functions of apoE.
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              Current understanding of Alzheimer’s disease diagnosis and treatment

              Alzheimer’s disease is the most common cause of dementia worldwide, with the prevalence continuing to grow in part because of the aging world population. This neurodegenerative disease process is characterized classically by two hallmark pathologies: β-amyloid plaque deposition and neurofibrillary tangles of hyperphosphorylated tau. Diagnosis is based upon clinical presentation fulfilling several criteria as well as fluid and imaging biomarkers. Treatment is currently targeted toward symptomatic therapy, although trials are underway that aim to reduce the production and overall burden of pathology within the brain. Here, we discuss recent advances in our understanding of the clinical evaluation and treatment of Alzheimer’s disease, with updates regarding clinical trials still in progress.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                30 March 2020
                April 2020
                : 21
                : 7
                : 2381
                Affiliations
                Fujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases, Institute for Translational Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China; ganchenling@ 123456mail.fjmu.edu.cn (C.-L.G.); taozh@ 123456fjmu.edu.cn (T.Z.)
                Author notes
                [* ]Correspondence: leethres@ 123456hotmail.com or tlee0813@ 123456fjmu.edu.cn ; Tel.: +86-591-2286-2498
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0001-5968-1478
                Article
                ijms-21-02381
                10.3390/ijms21072381
                7178026
                32235595
                d9513b5c-0fbf-46f7-89d3-a11a3e892cbb
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 09 February 2020
                : 27 March 2020
                Categories
                Review

                Molecular biology
                alzheimer’s disease,amyloid precursor protein,presenilin,apolipoprotein e,chinese population

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