Please wait a minute...
 Home  About the Journal Editorial Board Aims & Scope Peer Review Policy Subscription Contact us
Early Edition  //  Current Issue  //  Open Special Issues  //  Archives  //  Most Read  //  Most Downloaded  //  Most Cited
Aging and disease    2019, Vol. 10 Issue (6) : 1293-1301     DOI: 10.14336/AD.2018.1105
Review |
The Potential Markers of Circulating microRNAs and long non-coding RNAs in Alzheimer's Disease
Yanfang Zhao1,*, Yuan Zhang2, Lei Zhang2, Yanhan Dong2, Hongfang Ji1, Liang Shen1
1Institute of Biomedical Research, Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Zibo Key Laboratory of New Drug Development of Neurodegenerative diseases, School for Life Science, Shandong University of Technology, Zibo, China.
2Institute for Translational Medicine, Qingdao University, Qingdao, China.
Download: PDF(628 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks    

Alzheimer’s disease (AD) is a neurodegenerative disorder and one of the leading causes of disability and mortality in the late life with no curative treatment currently. Thus, it is urgently to establish sensitive and non-invasive biomarkers for AD diagnosis, particularly in the early stage. Recently, emerging number of microRNAs (miRNAs) and long-noncoding RNAs (lncRNAs) are considered as effective biomarkers in various diseases as they possess characteristics of stable, resistant to RNAase digestion and many extreme conditions in circulatory fluid. This review highlights recent advances in the identification of the aberrantly expressed miRNAs and lncRNAs in circulatory network for detection of AD. We summarized the abnormal expressed miRNAs in blood and cerebrospinal fluid (CSF), and detailed discussed the functions and molecular mechanism of serum or plasma miRNAs-miR-195, miR-155, miR-34a, miR-9, miR-206, miR-125b and miR-29 in the regulation of AD progression. In addition, we also elaborated the role of circulating lncRNA major including beta-site APP cleaving enzyme 1 (BACE1) and its antisense lncRNA BACE1-AS in AD pathological advancement. In brief, confirming the aberrantly expressed circulating miRNAs and lncRNAs will provide an effective testing tools for treatment of AD in the future.

Keywords Alzheimer’s disease      circulating      miRNA      lncRNA     
Corresponding Authors: Zhao Yanfang   
About author: These are co-senior authors.
Just Accepted Date: 13 November 2018   Issue Date: 16 November 2019
E-mail this article
E-mail Alert
Articles by authors
Zhao Yanfang
Zhang Yuan
Zhang Lei
Dong Yanhan
Ji Hongfang
Shen Liang
Cite this article:   
Zhao Yanfang,Zhang Yuan,Zhang Lei, et al. The Potential Markers of Circulating microRNAs and long non-coding RNAs in Alzheimer's Disease[J]. Aging and disease, 2019, 10(6): 1293-1301.
URL:     OR
Figure 1.  Circulating biomarkers in AD pathological condition. Plasma/serum biomarkers including miRNAs and lncRNAs, and cerebrospinal fluid (CSF) miRNAs.
[1] Reitz C, Mayeux R (2014). Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers. Biochem Pharmacol, 88:640-651.
[2] Sumner IL, Edwards RA, Asuni AA, Teeling JL (2018). Antibody Engineering for Optimized Immunotherapy in Alzheimer's Disease. Front Neurosci, 12:254.
[3] Jarrell JT, Gao L, Cohen DS, Huang X (2018). Network Medicine for Alzheimer's Disease and Traditional Chinese Medicine. Molecules, 23.
[4] Magalingam KB, Radhakrishnan A, Ping NS, Haleagrahara N (2018). Current Concepts of Neurodegenerative Mechanisms in Alzheimer's Disease. Biomed Res Int, 2018: 3740461.
[5] Kumar A, Singh A, Ekavali (2015). A review on Alzheimer's disease pathophysiology and its management: an update. Pharmacol Rep, 67:195-203.
[6] Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, et al. (2017). Dementia prevention, intervention, and care. Lancet, 390:2673-2734.
[7] Prince MJ, Wu F, Guo Y, Gutierrez Robledo LM, O'Donnell M, Sullivan R, et al. (2015). The burden of disease in older people and implications for health policy and practice. Lancet, 385:549-562.
[8] Bartel DP (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116:281-297.
[9] Tan L, Yu JT, Tan L (2015). Causes and Consequences of MicroRNA Dysregulation in Neurodegenerative Diseases. Mol Neurobiol, 51:1249-1262.
[10] Baldassarre A, Felli C, Prantera G, Masotti A (2017). Circulating microRNAs and Bioinformatics Tools to Discover Novel Diagnostic Biomarkers of Pediatric Diseases. Genes (Basel), 8.
[11] Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ, et al. (2010). The microRNA spectrum in 12 body fluids. Clin Chem, 56:1733-1741.
[12] Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, et al. (2008). Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res, 18:997-1006.
[13] Yang TT, Liu CG, Gao SC, Zhang Y, Wang PC (2018). The Serum Exosome Derived MicroRNA-135a, -193b, and -384 Were Potential Alzheimer's Disease Biomarkers. Biomed Environ Sci, 31:87-96.
[14] Kumar S, Reddy PH (2018). MicroRNA-455-3p as a Potential Biomarker for Alzheimer's Disease: An Update. Front Aging Neurosci, 10:41.
[15] Wu Y, Xu J, Xu J, Cheng J, Jiao D, Zhou C, et al. (2017). Lower Serum Levels of miR-29c-3p and miR-19b-3p as Biomarkers for Alzheimer's Disease. Tohoku J Exp Med, 242:129-136.
[16] Chen J, Qi Y, Liu CF, Lu JM, Shi J, Shi Y (2018). MicroRNA expression data analysis to identify key miRNAs associated with Alzheimer's disease. J Gene Med, 20:e3014.
[17] Xie B, Liu Z, Jiang L, Liu W, Song M, Zhang Q, et al. (2017). Increased Serum miR-206 Level Predicts Conversion from Amnestic Mild Cognitive Impairment to Alzheimer's Disease: A 5-Year Follow-up Study. J Alzheimers Dis, 55:509-520.
[18] Jia LH, Liu YN (2016). Downregulated serum miR-223 servers as biomarker in Alzheimer's disease. Cell Biochem Funct, 34:233-237.
[19] Wu Q, Ye X, Xiong Y, Zhu H, Miao J, Zhang W, et al. (2016). The Protective Role of microRNA-200c in Alzheimer's Disease Pathologies Is Induced by Beta Amyloid-Triggered Endoplasmic Reticulum Stress. Front Mol Neurosci, 9:140.
[20] Sorensen SS, Nygaard AB, Christensen T (2016). miRNA expression profiles in cerebrospinal fluid and blood of patients with Alzheimer's disease and other types of dementia - an exploratory study. Transl Neurodegener, 5:6.
[21] Hara N, Kikuchi M, Miyashita A, Hatsuta H, Saito Y, Kasuga K, et al. (2017). Serum microRNA miR-501-3p as a potential biomarker related to the progression of Alzheimer's disease. Acta Neuropathol Commun, 5:10.
[22] Zhang Y, Xing H, Guo S, Zheng Z, Wang H, Xu D (2016). MicroRNA-135b has a neuroprotective role via targeting of beta-site APP-cleaving enzyme 1. Exp Ther Med, 12:809-814.
[23] Cosin-Tomas M, Antonell A, Llado A, Alcolea D, Fortea J, Ezquerra M, et al. (2017). Plasma miR-34a-5p and miR-545-3p as Early Biomarkers of Alzheimer's Disease: Potential and Limitations. Mol Neurobiol, 54:5550-5562.
[24] Hong H, Li Y, Su B (2017). Identification of Circulating miR-125b as a Potential Biomarker of Alzheimer's Disease in APP/PS1 Transgenic Mouse. J Alzheimers Dis, 59:1449-1458.
[25] Zhang R, Zhou H, Jiang L, Mao Y, Cui X, Xie B, et al. (2016). MiR-195 dependent roles of mitofusin2 in the mitochondrial dysfunction of hippocampal neurons in SAMP8 mice. Brain Res, 1652:135-143.
[26] Vetrivel KS, Barman A, Chen Y, Nguyen PD, Wagner SL, Prabhakar R, et al. (2011). Loss of cleavage at beta'-site contributes to apparent increase in beta-amyloid peptide (Abeta) secretion by beta-secretase (BACE1)-glycosylphosphatidylinositol (GPI) processing of amyloid precursor protein. J Biol Chem, 286:26166-26177.
[27] Zhu HC, Wang LM, Wang M, Song B, Tan S, Teng JF, et al. (2012). MicroRNA-195 downregulates Alzheimer's disease amyloid-beta production by targeting BACE1. Brain Res Bull, 88:596-601.
[28] Sun LH, Ban T, Liu CD, Chen QX, Wang X, Yan ML, et al. (2015). Activation of Cdk5/p25 and tau phosphorylation following chronic brain hypoperfusion in rats involves microRNA-195 down-regulation. J Neurochem, 134:1139-1151.
[29] Rubio-Perez JM, Morillas-Ruiz JM (2012). A review: inflammatory process in Alzheimer's disease, role of cytokines. Scientific World Journal, 2012:756357.
[30] Falcao AS, Carvalho LA, Lidonio G, Vaz AR, Lucas SD, Moreira R, et al. (2017). Dipeptidyl Vinyl Sulfone as a Novel Chemical Tool to Inhibit HMGB1/NLRP3-Inflammasome and Inflamma-miRs in Abeta-Mediated Microglial Inflammation. ACS Chem Neurosci, 8:89-99.
[31] Fernandes A, Ribeiro AR, Monteiro M, Garcia G, Vaz AR, Brites D (2018). Secretome from SH-SY5Y APPSwe cells trigger time-dependent CHME3 microglia activation phenotypes, ultimately leading to miR-21 exosome shuttling. Biochimie.
[32] Guedes JR, Custodia CM, Silva RJ, de Almeida LP, Pedroso de Lima MC, Cardoso AL (2014). Early miR-155 upregulation contributes to neuroinflammation in Alzheimer's disease triple transgenic mouse model. Hum Mol Genet, 23:6286-6301.
[33] Guedes JR, Santana I, Cunha C, Duro D, Almeida MR, Cardoso AM, et al. (2016). MicroRNA deregulation and chemotaxis and phagocytosis impairment in Alzheimer's disease. Alzheimers Dement (Amst), 3:7-17.
[34] Henry CJ, Huang Y, Wynne AM, Godbout JP (2009). Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1beta and anti-inflammatory IL-10 cytokines. Brain Behav Immun, 23:309-317.
[35] Li JJ, Wang B, Kodali MC, Chen C, Kim E, Patters BJ, et al. (2018). In vivo evidence for the contribution of peripheral circulating inflammatory exosomes to neuroinflammation. J Neuroinflammation, 15:8.
[36] Song J, Lee JE (2015). miR-155 is involved in Alzheimer's disease by regulating T lymphocyte function. Front Aging Neurosci, 7:61.
[37] Schipper HM, Maes OC, Chertkow HM, Wang E (2007). MicroRNA expression in Alzheimer blood mononuclear cells. Gene Regul Syst Bio, 1:263-274.
[38] Sarkar S, Jun S, Rellick S, Quintana DD, Cavendish JZ, Simpkins JW (2016). Expression of microRNA-34a in Alzheimer's disease brain targets genes linked to synaptic plasticity, energy metabolism, and resting state network activity. Brain Res, 1646:139-151.
[39] Wang X, Liu P, Zhu H, Xu Y, Ma C, Dai X, et al. (2009). miR-34a, a microRNA up-regulated in a double transgenic mouse model of Alzheimer's disease, inhibits bcl2 translation. Brain Res Bull, 80:268-273.
[40] Jian C, Lu M, Zhang Z, Liu L, Li X, Huang F, et al. (2017). miR-34a knockout attenuates cognitive deficits in APP/PS1 mice through inhibition of the amyloidogenic processing of APP. Life Sci, 182:104-111.
[41] Li LH, Tu QY, Deng XH, Xia J, Hou DR, Guo K, et al. (2017). Mutant presenilin2 promotes apoptosis through the p53/miR-34a axis in neuronal cells. Brain Res, 1662:57-64.
[42] Agostini M, Tucci P, Killick R, Candi E, Sayan BS, Rivetti di Val Cervo P, et al. (2011). Neuronal differentiation by TAp73 is mediated by microRNA-34a regulation of synaptic protein targets. Proc Natl Acad Sci U S A, 108:21093-21098.
[43] Yilmaz SG, Erdal ME, Ozge AA, Sungur MA (2016). Can Peripheral MicroRNA Expression Data Serve as Epigenomic (Upstream) Biomarkers of Alzheimer's Disease? OMICS, 20:456-461.
[44] Schonrock N, Humphreys DT, Preiss T, Gotz J (2012). Target gene repression mediated by miRNAs miR-181c and miR-9 both of which are down-regulated by amyloid-beta. J Mol Neurosci, 46:324-335.
[45] Chang F, Zhang LH, Xu WP, Jing P, Zhan PY (2014). microRNA-9 attenuates amyloidbeta-induced synaptotoxicity by targeting calcium/calmodulin-dependent protein kinase kinase 2. Mol Med Rep, 9:1917-1922.
[46] Li S, Yan Y, Jiao Y, Gao Z, Xia Y, Kong L, et al. (2016). Neuroprotective Effect of Osthole on Neuron Synapses in an Alzheimer's Disease Cell Model via Upregulation of MicroRNA-9. J Mol Neurosci, 60:71-81.
[47] Li SH, Gao P, Wang LT, Yan YH, Xia Y, Song J, et al. (2017). Osthole Stimulated Neural Stem Cells Differentiation into Neurons in an Alzheimer's Disease Cell Model via Upregulation of MicroRNA-9 and Rescued the Functional Impairment of Hippocampal Neurons in APP/PS1 Transgenic Mice. Front Neurosci, 11:340.
[48] Xie B, Zhou H, Zhang R, Song M, Yu L, Wang L, et al. (2015). Serum miR-206 and miR-132 as Potential Circulating Biomarkers for Mild Cognitive Impairment. J Alzheimers Dis, 45:721-731.
[49] Moon J, Lee ST, Kong IG, Byun JI, Sunwoo JS, Shin JW, et al. (2016). Early diagnosis of Alzheimer's disease from elevated olfactory mucosal miR-206 level. Sci Rep, 6:20364.
[50] Lee ST, Chu K, Jung KH, Kim JH, Huh JY, Yoon H, et al. (2012). miR-206 regulates brain-derived neurotrophic factor in Alzheimer disease model. Ann Neurol, 72:269-277.
[51] Tian N, Cao Z, Zhang Y (2014). MiR-206 decreases brain-derived neurotrophic factor levels in a transgenic mouse model of Alzheimer's disease. Neurosci Bull, 30:191-197.
[52] Wang CN, Wang YJ, Wang H, Song L, Chen Y, Wang JL, et al. (2017). The Anti-dementia Effects of Donepezil Involve miR-206-3p in the Hippocampus and Cortex. Biol Pharm Bull, 40:465-472.
[53] Galimberti D, Villa C, Fenoglio C, Serpente M, Ghezzi L, Cioffi SM, et al. (2014). Circulating miRNAs as potential biomarkers in Alzheimer's disease. J Alzheimers Dis, 42:1261-1267.
[54] Tan L, Yu JT, Liu QY, Tan MS, Zhang W, Hu N, et al. (2014). Circulating miR-125b as a biomarker of Alzheimer's disease. J Neurol Sci, 336:52-56.
[55] Lugli G, Cohen AM, Bennett DA, Shah RC, Fields CJ, Hernandez AG, et al. (2015). Plasma Exosomal miRNAs in Persons with and without Alzheimer Disease: Altered Expression and Prospects for Biomarkers. PLoS One, 10:e0139233.
[56] Micheli F, Palermo R, Talora C, Ferretti E, Vacca A, Napolitano M (2016). Regulation of proapoptotic proteins Bak1 and p53 by miR-125b in an experimental model of Alzheimer's disease: Protective role of 17beta-estradiol. Neurosci Lett, 629:234-240.
[57] Ma X, Liu L, Meng J (2017). MicroRNA-125b promotes neurons cell apoptosis and Tau phosphorylation in Alzheimer's disease. Neurosci Lett, 661:57-62.
[58] Banzhaf-Strathmann J, Benito E, May S, Arzberger T, Tahirovic S, Kretzschmar H, et al. (2014). MicroRNA-125b induces tau hyperphosphorylation and cognitive deficits in Alzheimer's disease. EMBO J, 33:1667-1680.
[59] Jin Y, Tu Q, Liu M (2018). MicroRNA125b regulates Alzheimer's disease through SphK1 regulation. Mol Med Rep, 18:2373-2380.
[60] Villa C, Ridolfi E, Fenoglio C, Ghezzi L, Vimercati R, Clerici F, et al. (2013). Expression of the transcription factor Sp1 and its regulatory hsa-miR-29b in peripheral blood mononuclear cells from patients with Alzheimer's disease. J Alzheimers Dis, 35:487-494.
[61] Pereira PA, Tomas JF, Queiroz JA, Figueiras AR, Sousa F (2016). Recombinant pre-miR-29b for Alzheimer s disease therapeutics. Sci Rep, 6:19946.
[62] Yang G, Song Y, Zhou X, Deng Y, Liu T, Weng G, et al. (2015). MicroRNA-29c targets beta-site amyloid precursor protein-cleaving enzyme 1 and has a neuroprotective role in vitro and in vivo. Mol Med Rep, 12:3081-3088.
[63] Lei X, Lei L, Zhang Z, Zhang Z, Cheng Y (2015). Downregulated miR-29c correlates with increased BACE1 expression in sporadic Alzheimer's disease. Int J Clin Exp Pathol, 8:1565-1574.
[64] Shioya M, Obayashi S, Tabunoki H, Arima K, Saito Y, Ishida T, et al. (2010). Aberrant microRNA expression in the brains of neurodegenerative diseases: miR-29a decreased in Alzheimer disease brains targets neurone navigator 3. Neuropathol Appl Neurobiol, 36:320-330.
[65] Zong Y, Yu P, Cheng H, Wang H, Wang X, Liang C, et al. (2015). miR-29c regulates NAV3 protein expression in a transgenic mouse model of Alzheimer's disease. Brain Res, 1624:95-102.
[66] Ghidoni R, Benussi L, Paterlini A, Albertini V, Binetti G, Emanuele E (2011). Cerebrospinal fluid biomarkers for Alzheimer's disease: the present and the future. Neurodegener Dis, 8:413-420.
[67] Derkow K, Rossling R, Schipke C, Kruger C, Bauer J, Fahling M, et al. (2018). Distinct expression of the neurotoxic microRNA family let-7 in the cerebrospinal fluid of patients with Alzheimer's disease. PLoS One, 13:e0200602.
[68] Liu Y, He X, Li Y, Wang T (2018). Cerebrospinal fluid CD4+ T lymphocyte-derived miRNA-let-7b can enhances the diagnostic performance of Alzheimer's disease biomarkers. Biochem Biophys Res Commun, 495:1144-1150.
[69] Muller M, Jakel L, Bruinsma IB, Claassen JA, Kuiperij HB, Verbeek MM (2016). MicroRNA-29a Is a Candidate Biomarker for Alzheimer's Disease in Cell-Free Cerebrospinal Fluid. Mol Neurobiol, 53:2894-2899.
[70] Li W, Li X, Xin X, Kan PC, Yan Y (2016). MicroRNA-613 regulates the expression of brain-derived neurotrophic factor in Alzheimer's disease. Biosci Trends, 10:372-377.
[71] Dangla-Valls A, Molinuevo JL, Altirriba J, Sanchez-Valle R, Alcolea D, Fortea J, et al. (2017). CSF microRNA Profiling in Alzheimer's Disease: a Screening and Validation Study. Mol Neurobiol, 54:6647-6654.
[72] Liu CG, Wang JL, Li L, Xue LX, Zhang YQ, Wang PC (2014). MicroRNA-135a and -200b, potential Biomarkers for Alzheimers disease, regulate beta secretase and amyloid precursor protein. Brain Res, 1583:55-64.
[73] Liu CG, Song J, Zhang YQ, Wang PC (2014). MicroRNA-193b is a regulator of amyloid precursor protein in the blood and cerebrospinal fluid derived exosomal microRNA-193b is a biomarker of Alzheimer's disease. Mol Med Rep, 10:2395-2400.
[74] Zhang Y, Liu C, Wang J, Li Q, Ping H, Gao S, et al. (2016). MiR-299-5p regulates apoptosis through autophagy in neurons and ameliorates cognitive capacity in APPswe/PS1dE9 mice. Sci Rep, 6:24566.
[75] Yang G, Song Y, Zhou X, Deng Y, Liu T, Weng G, et al. (2015). DNA methyltransferase 3, a target of microRNA-29c, contributes to neuronal proliferation by regulating the expression of brain-derived neurotrophic factor. Mol Med Rep, 12:1435-1442.
[76] Sala Frigerio C, Lau P, Salta E, Tournoy J, Bossers K, Vandenberghe R, et al. (2013). Reduced expression of hsa-miR-27a-3p in CSF of patients with Alzheimer disease. Neurology, 81:2103-2106.
[77] Zhu Y, Li C, Sun A, Wang Y, Zhou S (2015). Quantification of microRNA-210 in the cerebrospinal fluid and serum: Implications for Alzheimer's disease. Exp Ther Med, 9:1013-1017.
[78] Liu CG, Wang JL, Li L, Wang PC (2014). MicroRNA-384 regulates both amyloid precursor protein and beta-secretase expression and is a potential biomarker for Alzheimer's disease. Int J Mol Med, 34:160-166.
[79] Zhang Y, Li Q, Liu C, Gao S, Ping H, Wang J, et al. (2016). MiR-214-3p attenuates cognition defects via the inhibition of autophagy in SAMP8 mouse model of sporadic Alzheimer's disease. Neurotoxicology, 56:139-149.
[80] Jiang X, Lei R, Ning Q (2016). Circulating long noncoding RNAs as novel biomarkers of human diseases. Biomark Med, 10:757-769.
[81] Lee C, Kikyo N (2012). Strategies to identify long noncoding RNAs involved in gene regulation. Cell Biosci, 2:37.
[82] Ponting CP, Oliver PL, Reik W (2009). Evolution and functions of long noncoding RNAs. Cell, 136:629-641.
[83] Lee DY, Moon J, Lee ST, Jung KH, Park DK, Yoo JS, et al. (2015). Distinct Expression of Long Non-Coding RNAs in an Alzheimer's Disease Model. J Alzheimers Dis, 45:837-849.
[84] Fang M, Zhang P, Zhao Y, Liu X (2017). Bioinformatics and co-expression network analysis of differentially expressed lncRNAs and mRNAs in hippocampus of APP/PS1 transgenic mice with Alzheimer disease. Am J Transl Res, 9:1381-1391.
[85] Feng L, Liao YT, He JC, Xie CL, Chen SY, Fan HH, et al. (2018). Plasma long non-coding RNA BACE1 as a novel biomarker for diagnosis of Alzheimer disease. BMC Neurol, 18:4.
[86] Manzine PR, Souza MDS, Cominetti MR (2016). BACE1 levels are increased in plasma of Alzheimer's disease patients compared with matched cognitively healthy controls. Per Med, 13:531-540.
[87] Herrera-Rivero M, Elena Hernandez-Aguilar M, Emiliano Aranda-Abreu G (2015). A strategy focused on MAPT, APP, NCSTN and BACE1 to build blood classifiers for Alzheimer's disease. J Theor Biol, 376:32-38.
[88] Faghihi MA, Modarresi F, Khalil AM, Wood DE, Sahagan BG, Morgan TE, et al. (2008). Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase. Nat Med, 14:723-730.
[89] Kang MJ, Abdelmohsen K, Hutchison ER, Mitchell SJ, Grammatikakis I, Guo R, et al. (2014). HuD regulates coding and noncoding RNA to induce APP-->Abeta processing. Cell Rep, 7:1401-1409.
[90] Mazdeh M, Komaki A, Omrani MD, Gharzi V, Sayad A, Taheri M, et al. (2018). Expression analysis of beta-secretase 1 (BACE1) and its naturally occurring antisense (BACE1-AS) in blood of epileptic patients. Neurol Sci, 39:1565-1569.
[91] Wang P, Zheng X, Guo Q, Yang P, Pang X, Qian K, et al. (2018). Systemic delivery of BACE1 siRNA through neuron-targeted nanocomplexes for treatment of Alzheimer's disease. J Control Release, 279:220-233.
[92] Sakamoto K, Matsuki S, Matsuguma K, Yoshihara T, Uchida N, Azuma F, et al. (2017). BACE1 Inhibitor Lanabecestat (AZD3293) in a Phase 1 Study of Healthy Japanese Subjects: Pharmacokinetics and Effects on Plasma and Cerebrospinal Fluid Abeta Peptides. J Clin Pharmacol, 57:1460-1471.
[93] Lashley T, Schott JM, Weston P, Murray CE, Wellington H, Keshavan A, et al. (2018). Molecular biomarkers of Alzheimer's disease: progress and prospects. Dis Model Mech, 11.
[1] Zhang Jie, Wang Lijun, Deng Xia, Fei Guoqiang, Jin Lirong, Pan Xiaoli, Cai Liuhan, Albano Anthony D, Zhong Chunjiu. Five-Minute Cognitive Test as A New Quick Screening of Cognitive Impairment in The Elderly[J]. Aging and disease, 2019, 10(6): 1258-1269.
[2] Gronek Piotr, Balko Stefan, Gronek Joanna, Zajac Adam, Maszczyk Adam, Celka Roman, Doberska Agnieszka, Czarny Wojciech, Podstawski Robert, Clark Cain C. T, Yu Fang. Physical Activity and Alzheimer’s Disease: A Narrative Review[J]. Aging and disease, 2019, 10(6): 1282-1292.
[3] Yingnan Xue, Zhenhua Zhang, Caiyun Wen, Huiru Liu, Suyuan Wang, Jiance Li, Qichuan Zhuge, Weijian Chen, Qiong Ye. Characterization of Alzheimer’s Disease Using Ultra-high b-values Apparent Diffusion Coefficient and Diffusion Kurtosis Imaging[J]. Aging and disease, 2019, 10(5): 1026-1036.
[4] Xiao-Li Zhou, Meng-Bei Xu, Ting-Yu Jin, Pei-Qing Rong, Guo-Qing Zheng, Yan Lin. Preclinical Evidence and Possible Mechanisms of Extracts or Compounds from Cistanches for Alzheimer’s Disease[J]. Aging and disease, 2019, 10(5): 1075-1093.
[5] Zhi-Ying Tian, Chun-Yan Wang, Tao Wang, Yan-Chun Li, Zhan-You Wang. Glial S100A6 Degrades β-amyloid Aggregation through Targeting Competition with Zinc Ions[J]. Aging and disease, 2019, 10(4): 756-769.
[6] Takehiko Yamanaka, Yuto Uchida, Keita Sakurai, Daisuke Kato, Masayuki Mizuno, Toyohiro Sato, Yuta Madokoro, Yuko Kondo, Ayuko Suzuki, Yoshino Ueki, Fumiyasu Ishii, Cesar V Borlongan, Noriyuki Matsukawa. Anatomical Links between White Matter Hyperintensity and Medial Temporal Atrophy Reveal Impairment of Executive Functions[J]. Aging and disease, 2019, 10(4): 711-718.
[7] Yu-Sheng Li, Zhi-Hua Yang, Yao Zhang, Jing Yang, Dan-Dan Shang, Shu-Yu Zhang, Jun Wu, Yan Ji, Lu Zhao, Chang-He Shi, Yu-Ming Xu. Two Novel Mutations and a de novo Mutation in PSEN1 in Early-onset Alzheimer’s Disease[J]. Aging and disease, 2019, 10(4): 908-914.
[8] Qing-Qing Tao, Yu-Chao Chen, Zhi-Ying Wu. The role of CD2AP in the Pathogenesis of Alzheimer's Disease[J]. Aging and disease, 2019, 10(4): 901-907.
[9] Christopher Bi, Stephanie Bi, Bin Li. Processing of Mutant β-Amyloid Precursor Protein and the Clinicopathological Features of Familial Alzheimer’s Disease[J]. Aging and disease, 2019, 10(2): 383-403.
[10] Seong Gak Jeon, Eun Ji Song, Dongje Lee, Junyong Park, Yunkwon Nam, Jin-il Kim, Minho Moon. Traditional Oriental Medicines and Alzheimer’s Disease[J]. Aging and disease, 2019, 10(2): 307-328.
[11] Yuan Zhang, Lei Zhang, Yu Wang, Han Ding, Sheng Xue, Hongzhao Qi, Peifeng Li. MicroRNAs or Long Noncoding RNAs in Diagnosis and Prognosis of Coronary Artery Disease[J]. Aging and disease, 2019, 10(2): 353-366.
[12] Ashok K. Shetty, Raghavendra Upadhya, Leelavathi N. Madhu, Maheedhar Kodali. Novel Insights on Systemic and Brain Aging, Stroke, Amyotrophic Lateral Sclerosis, and Alzheimer’s Disease[J]. Aging and disease, 2019, 10(2): 470-482.
[13] Jong Bin Bae,Ji Won Han,Kyung Phil Kwak,Bong Jo Kim,Shin Gyeom Kim,Jeong Lan Kim,Tae Hui Kim,Seung-Ho Ryu,Seok Woo Moon,Joon Hyuk Park,Jong Chul Youn,Dong Young Lee,Dong Woo Lee,Seok Bum Lee,Jung Jae Lee,Jin Hyeong Jhoo,Ki Woong Kim. Is Dementia More Fatal Than Previously Estimated? A Population-based Prospective Cohort Study[J]. Aging and disease, 2019, 10(1): 1-11.
[14] Antonina Luca, Carmela Calandra, Maria Luca. Molecular Bases of Alzheimer’s Disease and Neurodegeneration: The Role of Neuroglia[J]. Aging and disease, 2018, 9(6): 1134-1152.
[15] Sone Daichi, Imabayashi Etsuko, Maikusa Norihide, Ogawa Masayo, Sato Noriko, Matsuda Hiroshi, Japanese-Alzheimer’s Disease Neuroimaging Initiative. Voxel-based Specific Regional Analysis System for Alzheimer’s Disease (VSRAD) on 3-tesla Normal Database: Diagnostic Accuracy in Two Independent Cohorts with Early Alzheimer’s Disease[J]. Aging and disease, 2018, 9(4): 755-760.
Full text



Copyright © 2014 Aging and Disease, All Rights Reserved.
Address: Aging and Disease Editorial Office 3400 Camp Bowie Boulevard Fort Worth, TX76106 USA
Fax: (817) 735-0408 E-mail:
Powered by Beijing Magtech Co. Ltd