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Current Alzheimer Research


ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Research Article

Change in INSR, APBA2 and IDE Gene Expressions in Brains of Alzheimer's Disease Patients

Author(s): Isabela Bazzo da Costa, Roger Willian de Labio, Lucas Trevizani Rasmussen, Gustavo Arruda Viani, Elizabeth Chen, Joao Villares, Gustavo Turecki, Marilia de Arruda Cardoso Smith and Spencer L. M. Payao*

Volume 14 , Issue 7 , 2017

Page: [760 - 765] Pages: 6

DOI: 10.2174/1567205014666170203100734

Price: $65


Background: Alzheimer's disease (AD) is defined as a progressive and irreversible neurodegenerative disorder, the onset of which is mainly characterized by decreased cognition, memory loss, and mental confusion.

Objective: This study sought to quantify mRNA expression of the APBA2, INSR and IDE genes in brain samples from patients with AD and controls.

Methods: We investigated the mRNA expression of the APBA2, INSR and IDE genes in 150 RNA samples from entorhinal cortex, auditory cortex, and the hippocampus of individuals with AD and elderly controls using real time PCR. APOE genotypes were determined by PCR-RFLP.

Results: When the total brain samples were analyzed collectively, a decrease in IDE gene expression was found in AD patients relative to healthy elderly controls. However, when the samples were analyzed separately according to the region of the brain, there was a significant upregulation of INSR expression in the hippocampus and the entorhinal cortex in the AD patient group. We did not observe any statistical differences when gene expression was compared in the different regions of the brain of AD patients. When the E4 allele of apolipoprotein-E was considered in AD patients, the presence of this allele was found to be associated with decreased APBA2 gene expression. The same analysis using the INSR and IDE genes showed no significant statistical differences.

Conclusion: These results support the hypothesis that APBA2, IDE, and particularly INSR gene expression in different areas of Alzheimer’s patient’s brains could represent new markers for use in clinical diagnoses in the near future.

Keywords: Alzheimer's disease, brain, APBA2, INSR, IDE, gene expression.

Demarin V, Zavoreo I, Kes VB, Simundic AM. Biomarkers in Alzheimer’s disease. Clin Chem Lab Med 49(5): 773-8. (2011).
Prvulovic D, Hampel H. Amyloid beta (Abeta) and phospho-tau (p-tau) as diagnostic biomarkers in Alzheimer’s disease. Clin Chem Lab Med 49(3): 367-74. (2011).
Bloom GS. Amyloid-beta and tau: the trigger and bullet in Alzheimer disease pathogenesis. JAMA Neurol 71(4): 505-8. (2014).
Sutcliffe JS, Han MK, Amin T, Kesterson RA, Nurmi EL. Partial duplication of the APBA2 gene in chromosome 15q13 corresponds to duplicon structures. BMC Genomics 4(1): 15. (2003).
Taru H, Suzuki T. Facilitation of stress-induced phosphorylation of beta-amyloid precursor protein family members by X11-like/Mint2 protein. J Biol Chem 279(20): 21628-36. (2004).
Hao Y, Chai KH, McLoughlin DM, Chan HY, Lau KF. Promoter characterization and genomic organization of the human X11beta gene APBA2. Neuroreport 23(3): 146-51. (2012).
Lau KF, McLoughlin DM, Standen C, Miller CC. X11 alpha and x11 beta interact with presenilin-1 via their PDZ domains. Mol Cell Neurosci 16(5): 557-65. (2000).
Babatz TD, Kumar RA, Sudi J, Dobyns WB, Christian SL. Copy number and sequence variants implicate APBA2 as an autism candidate gene. Autism Res 2(6): 359-64. (2009).
Kirov G, Gumus D, Chen W. Norton N, Georgieva L, Sari M, et al. Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia. Hum Mol Genet 17(3): 458-65. (2008).
De Meyts P, Whittaker J. Structural biology of insulin and IGF1 receptors: implications for drug design. Nat Rev Drug Discov 1(10): 769-83. (2002).
Steen E, Terry BM, Rivera EJ. Cannon JL, Neely TR, Tavares R, et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease--is this type 3 diabetes? J Alzheimers Dis 7(1): 63-80. (2005).
Zhao WQ, Alkon DL. Role of insulin and insulin receptor in learning and memory. Mol Cell Endocrinol 177(1-2): 125-34. (2001).
Das P, Parsons AD, Scarborough J. Hoffman J, Wilson J, Thompson RN, et al. Electrophysiological and behavioral phenotype of insulin receptor defective mice. Physiol Behav 86(3): 287-96. (2005).
Cook DG, Leverenz JB, McMillan PJ, Kulstad JJ, Ericksen S, Roth RA, et al. Reduced hippocampal insulin-degrading enzyme in late-onset Alzheimer’s disease is associated with the apolipoprotein E-epsilon4 allele. Am J Pathol 162(1): 313-9. (2003).
Farris W, Mansourian S, Chang Y. Lindsley L, Eckman EA, Frosch MP, et al. Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc Natl Acad Sci USA 100(7): 4162-7. (2003).
Banks WA. The source of cerebral insulin. Eur J Pharmacol 490(1-3): 5-12. (2004).
Qiu WQ, Folstein MF. Insulin, insulin-degrading enzyme and amyloid-beta peptide in Alzheimer’s disease: Review and hypothesis. Neurobiol Aging 27(2): 190-8. (2006).
Trejo JL, Carro E, Garcia-Galloway E, Torres-Aleman I. Role of insulin-like growth factor I signaling in neurodegenerative diseases. J Mol Med 82(3): 156-62. (2004).
Hixson JE, Vernier DT. Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 31(3): 545-8. (1990).
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Methods 25(4): 402-8. (2001).
Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P. Risk of dementia in diabetes mellitus: A systematic review. Lancet Neurol 5(1): 64-74. (2006).
Fehm HL, Perras B, Smolnik R, Kern W, Born J. Manipulating neuropeptidergic pathways in humans: A novel approach to neuropharmacology? Eur J Pharmacol 405(1-3): 43-54. (2000).
Bai Z, Stamova B, Xu H, Ander BP, Wang J, Jickling GC, et al. Distinctive RNA expression profiles in blood associated with Alzheimer disease after accounting for white matter hyperintensities. Alzheimer Dis Assoc Disord 28(3): 226-33. (2014).
de la Monte SM, Wands JR. Alzheimer’s disease is type 3 diabetes-evidence reviewed. J Diabetes Sci Technol 2(6): 1101-13. (2008).
De Felice FG. Alzheimer’s disease and insulin resistance: translating basic science into clinical applications. J Clin Invest 123(2): 531-9. (2013).

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