Special Issue: Alzheimer’s disease

Khue Vu Nguyen; Khue Vu Nguyen

doi:10.3934/Neuroscience.2018.1.74

AIMS Neuroscience

2018, Volume 5, Issue 1: 74-80. doi: 10.3934/Neuroscience.2018.1.74

Previous Article Next Article

Editorial Special Issues

Special Issue: Alzheimer’s disease

Khue Vu Nguyen ^{1,2
,
,}

1.
Department of Medicine, Biochemical Genetics and Metabolism, The Mitochondrial and Metabolic Disease Center, School of Medicine, University of California, San Diego, Building CTF, Room C-103, 214 Dickinson Street, San Diego, CA 92103-8467, USA
2.
Department of Pediatrics, University of California, San Diego, School of Medicine, San Diego, La Jolla, CA 92093, USA

Received: 20 January 2018 Accepted: 22 January 2018 Published: 26 January 2018

More than 45 million people worldwide have Alzheimer’s disease (AD), a deterioration of memory and other cognitive domains that leads to death within 3 to 9 years after diagnosis. The principal risk factor for AD is age. As the aging population increases, the prevalence will approach 131 million cases worldwide in 2050. AD is therefore a global problem creating a rapidly growing epidemic and becoming a major threat to healthcare in our societies. It has been more than 20 years since it was first proposed that the neurodegeneration in AD may be caused by deposition of amyloid-b (Ab) peptides in plaques in brain tissue. According to the amyloid hypothesis, accumulation of Ab peptides, resulting from a chronic imbalance between Ab production and Ab clearance in the brain, is the primary influence driving AD pathogenesis. Current available medications appear to be able to produce moderate symptomatic benefits but not to stop disease progression. The search for biomarkers as well as novel therapeutic approaches for AD has been a major focus of research. Recent findings, however, show that neuronal-injury biomarkers are independent of Ab suggesting epigenetic modifications, gene-gene and/or gene-environment interactions in the disease etiology, and calling for reconsideration of the pathological cascade and assessment of alternative therapeutic strategies. In addition, recent research results regarding the expression of the β-amyloid precursor protein (APP) gene resulting in the presence of various APP-mRNA isoforms and their quantification, especially for identifying the most abundant one that may decisive for the normal status or disease risk, have been reported. As such, a more complete understanding of AD pathogenesis will likely require greater insights into the physiological function of the b-amyloid precursor protein (APP).
Citation: Khue Vu Nguyen. Special Issue: Alzheimer’s disease[J]. AIMS Neuroscience, 2018, 5(1): 74-80. doi: 10.3934/Neuroscience.2018.1.74

Related Papers:

Abstract

More than 45 million people worldwide have Alzheimer’s disease (AD), a deterioration of memory and other cognitive domains that leads to death within 3 to 9 years after diagnosis. The principal risk factor for AD is age. As the aging population increases, the prevalence will approach 131 million cases worldwide in 2050. AD is therefore a global problem creating a rapidly growing epidemic and becoming a major threat to healthcare in our societies. It has been more than 20 years since it was first proposed that the neurodegeneration in AD may be caused by deposition of amyloid-b (Ab) peptides in plaques in brain tissue. According to the amyloid hypothesis, accumulation of Ab peptides, resulting from a chronic imbalance between Ab production and Ab clearance in the brain, is the primary influence driving AD pathogenesis. Current available medications appear to be able to produce moderate symptomatic benefits but not to stop disease progression. The search for biomarkers as well as novel therapeutic approaches for AD has been a major focus of research. Recent findings, however, show that neuronal-injury biomarkers are independent of Ab suggesting epigenetic modifications, gene-gene and/or gene-environment interactions in the disease etiology, and calling for reconsideration of the pathological cascade and assessment of alternative therapeutic strategies. In addition, recent research results regarding the expression of the β-amyloid precursor protein (APP) gene resulting in the presence of various APP-mRNA isoforms and their quantification, especially for identifying the most abundant one that may decisive for the normal status or disease risk, have been reported. As such, a more complete understanding of AD pathogenesis will likely require greater insights into the physiological function of the b-amyloid precursor protein (APP).

References

[1]	World Alzheimer Report 2015.
[2]	Hardy JA, Higgin GA (1992) Alzheimer's disease: the amyloid cascade hypothesis. Science 256: 184–185. doi: 10.1126/science.1566067
[3]	Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol 8: 101–112.
[4]	Bettens K, Sleegers K, Van Broeckhoven C (2010) Current status on Alzheimer's disease molecular genetics: from past, to present, to future. Hum Mol Genet 19: R4–R11. doi: 10.1093/hmg/ddq142
[5]	Klafki HW (2006) Therapeutic approaches to Alzheimer's disease. Brain 129: 2840–2855. doi: 10.1093/brain/awl280
[6]	Hampel H, Frank R, Broich K, et al. (2010) Biomarkers for Alzheimer's disease: academic, industry and regulatory perspectives. Nat Rev 9: 560–574.
[7]	Jiang T, Yu JT, Zhu XC, et al. (2013) TREM2 in Alzheimer's disease. Mol Neurobiol 48: 180–185. doi: 10.1007/s12035-013-8424-8
[8]	Ulrich JD, Ulland TK, Colonna M, et al. (2017) Elucidating the role of TREM2 in Alzheimer's disease. Neuron 94: 237-248. doi: 10.1016/j.neuron.2017.02.042
[9]	Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297: 353–356. doi: 10.1126/science.1072994
[10]	Chetelat G (2013) Ab-independent processes-rethinking preclinical AD. Nat Rev Neurol 9: 123–124. doi: 10.1038/nrneurol.2013.21
[11]	Nguyen KV (2015) The human b-amyloid precursor protein: biomolecular and epigenetic aspects. BioMol Concepts 6: 11–32.
[12]	Wang SC, Oelze B, Schumacher A (2008) Age-specific epigenetic drift in late-onset Alzheimer's disease. PLoS One 3: e2698. doi: 10.1371/journal.pone.0002698
[13]	Combarros O, Cortina-Borja M, Smith AD, et al. (2009) Epistasis in sporadic Alzheimer's disease. Neurobiol Aging 30: 1333–1349. doi: 10.1016/j.neurobiolaging.2007.11.027
[14]	Nguyen KV (2014) Epigenetic regulation in amyloid precursor protein and the Lesch-Nyhan syndrome. Biochem Biophys Res Commun 446: 1091–1095. doi: 10.1016/j.bbrc.2014.03.062
[15]	Nguyen KV (2015) Epigenetic regulation in amyloid precursor protein with genomic rearrangements and the Lesch-Nyhan syndrome. Nucleosides Nucleotides Nucleic Acids 34: 674–690. doi: 10.1080/15257770.2015.1071844
[16]	Nguyen KV, Nyhan WL (2017) Quantification of various APP-mRNA isoforms and epistasis in Lesch-Nyhan disease. Neurosci Lett 643: 52–58. doi: 10.1016/j.neulet.2017.02.016
[17]	Nguyen KV, Leydiker K, Wang R, et al. (2017) A neurodevelopmental disorder with a nonsense mutation in the Ox-2 antigen domain of the amyloid precursor protein (APP) gene. Nucleosides Nucleotides Nucleic Acids 36: 317–327.
[18]	Ray B, Long JM, Sokol DK, et al. (2011) Increased secreted amyloid precursor protein-a (sAPPa) in severe autism: proposal of a specific, anabolic pathway and putative biomarker. PLoS One 6: e20405. doi: 10.1371/journal.pone.0020405
[19]	Sokol DK, Maloney B, Long JM, et al. (2011) Autism, Alzheimer's disease, and fragile X, APP, FMRP, and mGluR5 are molecular links. Neurology 76: 1344–1352. doi: 10.1212/WNL.0b013e3182166dc7
[20]	Bryson JB, Hobbs C, Parsons MJ, et al. (2012) Amyloid precursor protein (APP) contributes to pathology in the SOD^G93A mouse model of amyotrophic lateral sclerosis. Hum Mol Genet 21: 3871–3882. doi: 10.1093/hmg/dds215
[21]	Matias-Guiu JA, Oreja-Guevara C, Cabrera-Martin MN, et al. (2016) Amyloid proteins and their role in multiple sclerosis. Considerations in the use of amyloid-PET imaging. Front Neurol 7: 53.
[22]	Saonere JA (2011) Antisense therapy, a magic bullet for the treatment of various diseases: present and future prospects. J Med Genet Genomics 3: 77–83.
[23]	Sabaum JM, Weidermann A, Lemaire HG, et al. (1988) The promoter of Alzheimer's disease amyloid A4 precursor gene. EMBO J 7: 2807–2813.
[24]	Nicolas M, Hassan BA (2014) Amyloid precursor protein and neural development. Development 141: 2543–2548. doi: 10.1242/dev.108712

Reader Comments

Your name:*

Email:*
© 2018 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)