The Genetic Basis of AD Incidence and Treatment

: Alzheimer’s disease (AD) is caused by neuron death and is one of the diseases that cannot be cured under current medical technology. This review provides a summary of the relationship between the expression of three common AD-related gene variants (APP, PSEN1 and PSEN2) and the formation of abnormal Aβ and tau proteins aggregations (plaques and tangles). The possibility of using gene therapy to cure AD is also stated in this review. During research, several recent papers about gene-related AD are viewed. In those papers, researchers did experiment on transgenic mice and matched the results with markers of human AD to confirm that investigated gene variants are AD-related. However, mouse models cannot represent whole human AD characteristics, symptoms like language deficits cannot be investigated on mouse models. Furthermore, researches show that gene therapy such as overexpression of PGC-1α can eliminate AD-like symptoms in transgenic mouse models. It illustrates the potential of treating AD by using this type of gene therapy. Importantly, genetic technology is still under exploration before the safe application of gene therapy on humans due to possible unknown consequences of editing human genes.

[1]  C. Reitz,et al.  Early-Onset Alzheimer’s Disease: What Is Missing in Research? , 2021, Current Neurology and Neuroscience Reports.

[2]  T. Saido,et al.  Introduction of pathogenic mutations into the mouse Psen1 gene by Base Editor and Target-AID , 2018, Nature Communications.

[3]  Sangyun Jeong,et al.  Molecular and Cellular Basis of Neurodegeneration in Alzheimer’s Disease , 2017, Molecules and cells.

[4]  Nazanin Mirzaei,et al.  PPARγ-coactivator-1α gene transfer reduces neuronal loss and amyloid-β generation by reducing β-secretase in an Alzheimer’s disease model , 2016, Proceedings of the National Academy of Sciences.

[5]  M. Fändrich,et al.  Protein aggregation in Alzheimer’s disease: Aβ and τ and their potential roles in the pathogenesis of AD , 2015, Acta Neuropathologica.

[6]  T. Saido,et al.  New mouse model of Alzheimer's. , 2014, ACS chemical neuroscience.

[7]  A. Dale,et al.  What is normal in normal aging? Effects of aging, amyloid and Alzheimer's disease on the cerebral cortex and the hippocampus , 2014, Progress in Neurobiology.

[8]  Ze Yang,et al.  Apolipoprotein E, amyloid-beta, and neuroinflammation in Alzheimer’s disease , 2014, Neuroscience Bulletin.

[9]  R. Tanzi.  The genetics of Alzheimer disease. , 2012, Cold Spring Harbor perspectives in medicine.

[10]  M. Maeda,et al.  Presenilin-2 Mutation Causes Early Amyloid Accumulation and Memory Impairment in a Transgenic Mouse Model of Alzheimer's Disease , 2010, Journal of biomedicine & biotechnology.

[11]  Leonard Petrucelli,et al.  The role of tau in neurodegeneration , 2009, Molecular Neurodegeneration.

[12]  K. Yanagisawa.  [Risk factors for Alzheimer's disease]. , 2000, Rinsho shinkeigaku = Clinical neurology.

[13]  D. Selkoe.  Alzheimer's disease. , 2011, Cold Spring Harbor perspectives in biology.

[14]  N. Bogdanovic,et al.  PPARγ co-activator-1α (PGC-1α) reduces amyloid-β generation through a PPARγ-dependent mechanism. , 2011, Journal of Alzheimer's disease : JAD.