TY - JOUR
T1 - The Association of Essential Metals with APOE Genotype in Alzheimer's Disease
AU - Leko, Mirjana Babić
AU - Jurasović, Jasna
AU - Perković, Matea Nikolac
AU - Španić, Ena
AU - Sekovanić, Ankica
AU - Orct, Tatjana
AU - Škudar, Vesna Lukinović
AU - Baronica, Koraljka Bačić
AU - Kiđemet-Piskač, Spomenka
AU - Vogrinc, Željka
AU - Pivac, Nela
AU - Borovečki, Fran
AU - Hof, Patrick R.
AU - Šimić, Goran
N1 - Funding Information:
This work was funded by The Croatian Science Foundation grant IP-2019-04-3584 (“Role of blood-brain barrier, innate immunity, and tau protein oligomerization in the pathogenesis of Alzheimer’s disease”) to GSˇ and by the Scientific Centre of Excellence for Basic, Clinical and Translational Neuroscience CoRE-NEURO (“Experimental and clinical research of hypoxic-ischemic damage in perinatal and adult brain”; GA KK01.1.1.01.0007 funded by the European Union through the European Regional Development Fund), and in part by NIH grants P50 AG005138 and P30 AG066514 to PRH.
Publisher Copyright:
© 2021 - IOS Press. All rights reserved.
PY - 2021
Y1 - 2021
N2 - Background: The major confirmed genetic risk factor for late-onset, sporadic Alzheimer's disease (AD) is variant ϵ4 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. Objective: To test the association of essential metals with APOE genotype. 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. Results: Sodium, copper, and magnesium levels were increased in carriers of ϵ4 allele. Additionally, the increase in sodium, calcium and cobalt plasma levels was observed in carriers of ϵ4/ϵx genotype. The decrease in boron plasma levels was observed in carriers of ϵ4 allele and ϵ4/ϵ4 genotype. Additionally, CSF zinc levels as well as plasma sodium levels were increased in AD patients compared to HC. 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.
AB - Background: The major confirmed genetic risk factor for late-onset, sporadic Alzheimer's disease (AD) is variant ϵ4 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. Objective: To test the association of essential metals with APOE genotype. 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. Results: Sodium, copper, and magnesium levels were increased in carriers of ϵ4 allele. Additionally, the increase in sodium, calcium and cobalt plasma levels was observed in carriers of ϵ4/ϵx genotype. The decrease in boron plasma levels was observed in carriers of ϵ4 allele and ϵ4/ϵ4 genotype. Additionally, CSF zinc levels as well as plasma sodium levels were increased in AD patients compared to HC. 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.
KW - Alzheimer's disease
KW - Apolipoprotein E
KW - Copper
KW - Metals
KW - Mild cognitive impairment
KW - Zinc
UR - http://www.scopus.com/inward/record.url?scp=85111357972&partnerID=8YFLogxK
U2 - 10.3233/JAD-210158
DO - 10.3233/JAD-210158
M3 - Article
C2 - 34057084
AN - SCOPUS:85111357972
SN - 1387-2877
VL - 82
SP - 661
EP - 672
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 2
ER -