The Association of Essential Metals with APOE Genotype in Alzheimer’s Disease

Scientific paper - Original scientific paper

• Author: Mirjana Babić Leko
• Author: Jasna Jurasović
• Author: Matea Nikolac Perković
• Author: Ena Španić
• Author: Ankica Sekovanić
• Author: Tatjana Orct
• Author: Vesna Lukinović Škudar
• Author: Koraljka Bačić Baronica
• Author: Spomenka Kiđemet-Piskač
• Author: Željka Vogrinc
• Author: Nela Pivac
• Author: Fran Borovečki
• Author: Patrick R. Hof
• Author: Goran Šimić
• Author's institution: University of Zagreb; School of Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Neuroscience
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Neurology
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Human Physiology

Abstract (english)

Background: The major confirmed genetic risk factor for late-onset, sporadic Alzheimer's disease (AD) is variant ɛ4 of apolipoprotein E gene (APOE). It is proposed that ApoE, a protein involved in transport of cholesterol to neurons can cause neurodegeneration in AD through interaction with metals. Previous studies mostly associated copper, iron, zinc, and calcium with ApoE4-mediated toxicity.
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Objective: To test the association of essential metals with APOE genotype.
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Methods: We compared plasma and cerebrospinal fluid (CSF) levels of copper, zinc, iron, sodium, magnesium, calcium, cobalt, molybdenum, manganese, boron, and chromium, and CSF ferritin levels among AD, mild cognitive impairment (MCI) patients, and healthy controls (HC) with different APOE genotype.
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Results: Sodium, copper, and magnesium levels were increased in carriers of ɛ4 allele. Additionally, the increase in sodium, calcium and cobalt plasma levels was observed in carriers of ɛ4/ɛx genotype. The decrease in boron plasma levels was observed in carriers of ɛ4 allele and ɛ4/ɛ4 genotype. Additionally, CSF zinc levels as well as plasma sodium levels were increased in AD patients compared to HC.
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Conclusion: These results indicate that the molecular underpinnings of association of essential metals and metalloids with APOE should be further tested and clarified in vivo and in vitro.

• Keywords (english): Aged; Alzheimer Disease* / blood; Alzheimer Disease* / cerebrospinal fluid; Alzheimer Disease* / genetics; Apolipoprotein E4 / genetics*; Apolipoproteins E; Biological Transport / physiology; Cholesterol / metabolism; Cognitive Dysfunction / blood; Cognitive Dysfunction / cerebrospinal fluid; Cognitive Dysfunction / diagnosis; Correlation of Data; Female; Ferritins / cerebrospinal fluid; Genotype; Humans; Male; Metalloids* / blood; Metalloids* / cerebrospinal fluid; Metals* / blood; Metals* / cerebrospinal fluid; Metals* / classification; Sodium / blood*; Zinc / cerebrospinal fluid*
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Accepted version
• Journal title: Journal of Alzheimer's Disease
• Numbering: vol. 82, no. 2, pp. 661-672
• p-ISSN: 1387-2877
• e-ISSN: 1875-8908
• DOI: https://doi.org/10.3233/JAD-210158
• URN:NBN: urn:nbn:hr:105:247939
• Publication: 2021
• Document URL: https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/JAD-210158
• Type of resource: Text
• Access conditions: Open access
• Created on: 2022-01-11 11:29:23