Association of the apolipoprotein E ε4 allele in a Serbian population with Alzheimer’s dementia

Jelena Bašić; Vuk Milošević; Branka Đorđević; Nikola Stefanović; Marija Cvetković; Tatjana Jevtović Stoimenov; Ivana Stojanović

doi:10.2298/ABS230614026B

Authors

Jelena Bašić Department of Biochemistry, Faculty of Medicine, University of Niš, 18000 Niš, Serbia http://orcid.org/0000-0002-9221-561X
Vuk Milošević 1. Clinic of Neurology, University Clinical Center Niš, 18000 Niš, Serbia; 2. Faculty of Medicine, University of Niš, 18000 Niš, Serbia https://orcid.org/0000-0002-2434-8277
Branka Đorđević Department of Biochemistry, Faculty of Medicine, University of Niš, 18000 Niš, Serbia https://orcid.org/0000-0002-4521-1253
Nikola Stefanović Department of Pharmacy, Faculty of Medicine, University of Niš, 18000 Niš, Serbia https://orcid.org/0000-0003-2599-7508
Marija Cvetković Faculty of Medicine, University of Niš, 18000 Niš, Serbia https://orcid.org/0009-0007-4051-8858
Tatjana Jevtović Stoimenov Department of Biochemistry, Faculty of Medicine, University of Niš, 18000 Niš, Serbia https://orcid.org/0000-0003-0600-5411
Ivana Stojanović Department of Biochemistry, Faculty of Medicine, University of Niš, 18000 Niš, Serbia https://orcid.org/0000-0002-8835-9370

DOI:

https://doi.org/10.2298/ABS230614026B

Keywords:

Apolipoprotein E ε4, Alzheimer's disease, Dementia, rs429358, rs7412

Abstract

Paper description:

Single nucleotide polymorphisms rs429358 and rs7412 in the apolipoprotein E gene (APOE) are of great importance for APOEε2/ε3/ε4 carrier status determination.
APOEε2/ε3/ε4 allele carrier status in Alzheimer’s disease (AD) dementia and cognitively unimpaired subjects and the association of the APOEε4 allele with AD dementia risk in a Serbian population was assessed.
The APOEε4 allele was found to be associated with a higher risk of AD dementia compared to the reference ε3 allele.
This research is a potential contribution to improving diagnostic protocols for diagnosing and treating AD dementia in Serbia.

Abstract: Although single nucleotide polymorphisms rs429358 and rs7412 in the apolipoprotein E gene (APOE) are widely investigated to analyze APOE alleles, there are no data on their association with Alzheimer’s disease (AD) dementia in a Serbian population. This study aimed to investigate the distribution of APOE ε2/ε3/ε4 alleles in patients with dementia due to AD and cognitively unimpaired subjects and to assess the association of the APOE ε4 allele with disease risk in the Serbian population. A case-control study included patients with dementia due to AD and cognitively unimpaired individuals. APOE rs429358 and rs7412 were analyzed using the Real-Time PCR method with allele-specific TaqMan assays, followed by APOE ε2/ε3/ε4 allele carrier status analysis. Patients had a significantly higher frequency of the APOE ε4 allele than the control group (P<0.001). The APOE ε4 allele was found to be associated with a 3-fold higher risk of AD dementia compared to the reference ε3 allele (P<0.001). In conclusion, this is the first study to suggest that carriers of the APOE ε4 allele have a higher risk of developing dementia due to AD than those who carry the APOE ε3 allele in the Serbian population.

Downloads

Download data is not yet available.

References

Grujičić J, Nikolić A. Alzheimers disease: Epidemiological characteristics and its prevention. Health Care. 2021;50(2):57-72. https://doi.org/10.5937/zdravzast50-32931

Frisoni GB, Altomare D, Thal DR, Ribaldi F, van der Kant R, Ossenkoppele R, Blennow K, Cummings J, van Duijn C, Nilsson PM, Dietrich PY, Scheltens P, Dubois B. The probabilistic model of Alzheimer disease: the amyloid hypothesis revised. Nat Rev Neurosci. 2022;23(1):53-66. https://doi.org/10.1038/s41583-021-00533-w

Ando K, Houben S, Homa M, de Fisenne MA, Potier MC, Erneux C, Brion JP, Leroy K. Alzheimer’s Disease: Tau Pathology and Dysfunction of Endocytosis. Front Mol Neurosci. 2021;13:583755. https://doi.org/10.3389/fnmol.2020.583755

Prince MJ, Wimo A, Guerchet MM, Ali GC, Wu YT, Prina M. World Alzheimer Report 2015-The Global Impact of Dementia: An analysis of prevalence, incidence, cost and trends. London: Alzheimer’s Disease International; 2015. 82 p.

GBD 2016 Dementia Collaborators. Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(1):88-106. https://doi.org/10.1016/S1474-4422(18)30403-4

Troutwine BR, Hamid L, Lysaker CR, Strope TA, Wilkins HM. Apolipoprotein E and Alzheimer’s disease. Acta Pharm Sin B. 2022;12(2):496-510. https://doi.org/10.1016/j.apsb.2021.10.002

Transcript: APOE-201. Ensembl genome browser 104 for Human APOE gene [Internet]. EMBL-EBI. Ensembl release 104 - March 2023 [Cited 2023 May 14]. Available from: https://www.ensembl.org/Homo_sapiens/Transcript/ProteinSummary?db=core;g=ENSG00000130203;r=19:44905791-44909393;t=ENST00000252486

McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s Dement. 2011;7(3):263-9. https://doi.org/10.1016/j.jalz.2011.03.005

Milošević V, Malobabić M, Stojanović I, Bašić J. Importance of a functional measure in the evaluation of patients in a memory clinic: Validation of the Serbian version of the Amsterdam instrumental activities of daily living questionnaire. Clin Neurol Neurosurg. 2022;214:107165. https://doi.org/10.1016/j.clineuro.2022.107165

Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Feldman HH, Frisoni GB, Hampel H, Jagust WJ, Johnson KA, Knopman DS, Petersen RC, Scheltens P, Sperling RA, Dubois B. A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology. 2016;87(5):539-47. https://doi.org/10.1212/WNL.0000000000002923

Bachmeier C, Shackleton B, Ojo J, Paris D, Mullan M, Crawford F. Apolipoprotein E isoform-specific effects on lipoprotein receptor processing. Neuromolecular Med. 2014;16(4):686-96. https://doi.org/10.1007/s12017-014-8318-6

Iannucci J, Sen A, Grammas P. Isoform-Specific Effects of Apolipoprotein E on Markers of Inflammation and Toxicity in Brain Glia and Neuronal Cells In Vitro. Curr Issues Mol Biol. 2021;43(1):215-25. https://doi.org/10.3390/cimb43010018

Wang C, Najm R, Xu Q, Jeong DE, Walker D, Balestra ME, Yoon SY, Yuan H, Li G, Miller ZA, Miller BL, Malloy MJ, Huang Y. Gain of toxic apolipoprotein E4 effects in human iPSC-derived neurons is ameliorated by a small-molecule structure corrector. Nat Med. 2018;24(5):647-57. https://doi.org/10.1038/s41591-018-0004-z

Huebbe P, Rimbach G. Evolution of human apolipoprotein E (APOE) isoforms: Gene structure, protein function and interaction with dietary factors. Ageing Res Rev. 2017;37:146-61. https://doi.org/10.1016/j.arr.2017.06.002

Egert S, Rimbach G, Huebbe P. ApoE genotype: from geographic distribution to function and responsiveness to dietary factors. Proc Nutr Soc. 2012;71(3):410-24. https://doi.org/10.1017/S0029665112000249

Hu P, Qin YH, Jing CX, Lu L, Hu B, Du PF. Does the geographical gradient of ApoE4 allele exist in China? A systemic comparison among multiple Chinese populations. Mol Biol Rep. 2011;38(1):489-94. https://doi.org/10.1007/s11033-010-0132-0

Belloy ME, Napolioni V, Greicius MD. A Quarter Century of APOE and Alzheimer’s Disease: Progress to Date and the Path Forward. Neuron. 2019;101(5):820-838. https://doi.org/10.1016/j.neuron.2019.01.056

Saddiki H, Fayosse A, Cognat E, Sabia S, Engelborghs S, Wallon D, Alexopoulos P, Blennow K, Zetterberg H, Parnetti L, Zerr I, Hermann P, Gabelle A, Boada M, Orellana A, de Rojas I, Lilamand M, Bjerke M, Van Broeckhoven C, Farotti L, Salvadori N, Diehl-Schmid J, Grimmer T, Hourregue C, Dugravot A, Nicolas G, Laplanche JL, Lehmann S, Bouaziz-Amar E; Alzheimer’s Disease Neuroimaging Initiative; Hugon J, Tzourio C, Singh-Manoux A, Paquet C, Dumurgier J. Age and the association between apolipoprotein E genotype and Alzheimer disease: A cerebrospinal fluid biomarker-based case-control study. PLoS Med. 2020;17(8):e1003289. https://doi.org/10.1371/journal.pmed.1003289

Fray S, Achouri-Rassas A, Belal S, Messaoud T. Missing apolipoprotein E ε4 allele associated with nonamnestic Alzheimer's disease in a Tunisian population. J Genet. 2022;101:41. https://doi.org/10.1007/s12041-022-01384-9

Martínez S, Ochoa B, Pérez MR, Torrico F, García I, Garcia CC. Apolipoprotein E polymorphisms in adults over 60 years of age with mild cognitive impairment and Alzheimer's disease in different Venezuelan populations. Biomedica. 2022;42(Sp. 1):116-29. https://doi.org/10.7705/biomedica.5889

Halla SB, Tazzite A, Gazzaz B, El Moutawakil B, Dehbi H. Involvement of APOE polymorphism in Alzheimer's disease susceptibility and Donepezil response in Moroccan patients. Gene Reports. 2022;26:101484. https://doi.org/10.1016/j.genrep.2021.101484

Emrani S, Arain HA, DeMarshall C, Nuriel T. APOE4 is associated with cognitive and pathological heterogeneity in patients with Alzheimer’s disease: a systematic review. Alzheimer’ Res Ther. 2020;12(1):141. https://doi.org/10.1186/s13195-020-00712-4

Association of the apolipoprotein E ε4 allele in a Serbian population with Alzheimer’s dementia

Authors

DOI:

Keywords:

Abstract

Downloads

References

Downloads

Published

How to Cite

Issue

Section

License

Most read articles by the same author(s)

Current Issue

Make a Submission