Lower Plasma β-Amyloid 1-42 Levels in Amnestic Mild Cognitive Impairment Compared to Healthy Individuals
Abstract
BACKGROUND: Amnestic mild cognitive impairment (aMCI) is strongly associated with an increased risk of progression to Alzheimer’s disease (AD). In AD, cerebrospinal fluid (CSF) β-Amyloid 1-42 levels are known to decrease, a pattern which is also observed in aMCI. While in AD, apolipoprotein E (ApoE) ε4 allele is known to be a genetic risk factor, the role of ApoE ε4 allele in modulating plasma β-Amyloid 1-42 levels in aMCI remains unclear. Therefore, this study was performed to evaluate plasma β-Amyloid 1-42 levels in aMCI patients compared to cognitively healthy individuals and investigate its association with ApoE ε4 allele.
METHODS: A cross-sectional study involving 57 aMCI and 54 cognitively healthy control (HC) subjects was performed. Blood samples were taken from subjects from both groups for measurement of the plasma β-Amyloid 1-42 and ApoE ε4 allele. The plasma levels of β-Amyloid 1-42 were measured using an enzyme-linked immunosorbent assay (ELISA) methods, while the ApoE ε4 allele genotyping was conducted using polymerase chain reaction (PCR) techniques.
RESULTS: Plasma β-Amyloid 1-42 in individuals with aMCI (23.9 pg/mL) was significantly lower than that in HC (25.3 pg/mL) with cut-off value of 24.6 pg/mL (AUC: 70.8%; 95% CI: 61.1–80.5%; p<0.001) sensitivity of 64.8%, and specificity of 71.9%. There was no significant association between plasma β-Amyloid 1-42 and the ApoE ε4 allele. However, plasma β-Amyloid 1-42 in ε4 carriers were lower than in ε4 non-carriers.
CONCLUSION: Lower plasma β-Amyloid 1-42 levels were observed in aMCI patients compared to cognitively healthy individuals, suggesting its potential as a biomarker for identifying aMCI.
KEYWORDS: blood biomarkers, amyloid beta peptides, amnestic mild cognitive impairment (aMCI)
Full Text:
PDFReferences
Park JE, Choi KY, Kim BC, Choi SM, Song MK, Lee JJ, et al. Cerebrospinal fluid biomarkers for the diagnosis of prodromal alzheimer's disease in amnestic mild cognitive impairment. Dement Geriatr Cogn Dis Extra. 2019; 9(1): 100-13, CrossRef.
Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004; 256(3): 183-94, CrossRef.
Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, et al. Mild cognitive impairment - beyond controversies, towards a consensus: Report of the International Working Group on Mild Cognitive Impairment. J Intern Med. 2004; 256(3): 240-6, CrossRef.
Petersen RC, Roberts RO, Knopman DS, Boeve BF, Geda YE, Ivnik RJ, et al. Mild cognitive impairment: Ten years later. Arch Neurol. 2009; 66(12): 1447-55, CrossRef.
Risacher SL, Fandos N, Romero J, Sherriff I, Pesini P, Saykin AJ, et al. Plasma amyloid beta levels are associated with cerebral amyloid and tau deposition. Alzheimers Dement. 2019; 11: 510-9, CrossRef.
Saido TC. Metabolism of amyloid β peptide and pathogenesis of Alzheimer's disease. Proc Jpn Acad Ser B Phys Biol Sci. 2013; 89(7): 321-39, CrossRef.
Meiliana A, Wijaya A. The search for biomarkers in alzheimer's disease. Indones Biomed J. 2010; 2(1): 4-25, CrossRef.
Meiliana A, Dewi NM, Wijaya A. New insight in the molecular mechanisms of neurodegenerative disease. Indones Biomed J. 2018l 10(1): 16-24, CrossRef.
Ait-ghezala G, Abdullah L, Volmar CH, Paris D, Luis CA, Quadros A, et al. Diagnostic utility of APOE, soluble CD40, CD40L, and Abeta1-40 levels in plasma in alzheimer's disease. Cytokine. 2008; 44(2): 283-7, CrossRef.
Lopez OL, Kuller LH, Mehta PD, Becker JT, Gach HM, Sweet RA, et al. Plasma amyloid levels and the risk of AD in normal subjects in the cardiovascular health study. Neurology. 2008; 70(19): 1664-71, CrossRef.
Luis CA, Abdullah L, Paris D, Quadros A, Mullan M, Mouzon B, et al. Serum beta-amyloid correlates with neuropsychological impairment. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2009; 16(2): 203-18, CrossRef.
Pesini P, Perez-Grijalba V, Monleon I, Boada M, Tarraga L, Martinez-Lage P, et al. Reliable measurements of the beta-amyloid pool in blood could help in the early diagnosis of AD. Int J Alzheimers Dis. 2012; 2012: 604141, CrossRef.
Ruiz A, Pesini P, Espinosa A, Perez-Grijalba V, Valero S, Sotolongo-Grau O, et al. Blood amyloid beta levels in healthy, mild cognitive impairment and alzheimer's disease individuals: Replication of diastolic blood pressure correlations and analysis of critical covariates. PLoS One. 2013; 8(11): e81334, CrossRef.
Wang MJ, Yi S, Han JY, Park SY, Jang JW, Chun IK, et al. Oligomeric forms of amyloid-beta protein in plasma as a potential blood-based biomarker for Alzheimer's disease. Alzheimers Res Ther. 2017; 9(1): 98, CrossRef.
Graff-Radford NR, Crook JE, Lucas J, Boeve BF, Knopman DS, Ivnik RJ, et al. Association of low plasma Abeta42/Abeta40 ratios with increased imminent risk for mild cognitive impairment and alzheimer disease. Arch Neurol. 2007; 64(3): 354-62, CrossRef.
Hanon O, Vidal JS, Lehmann S, Bombois S, Allinquant B, Treluyer JM, et al. Plasma amyloid levels within the Alzheimer's process and correlations with central biomarkers. Alzheimers Dement. 2018; 14(7): 858-68, CrossRef.
Luis CA, Abdullah L, Paris D, Quadros A, Mullan M, Mouzon B, et al. Serum beta-amyloid correlates with neuropsychological impairment. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2009; 16(2): 203-18, CrossRef.
Leung R, Proitsi P, Simmons A, Lunnon K, Guntert A, Kronenberg D, et al. Inflammatory proteins in plasma are associated with severity of Alzheimer's disease. PLoS One. 2013; 8(6): e64971, CrossRef.
Sattlecker M, Khondoker M, Proitsi P, Williams S, Soininen H, Kloszewska I, et al. Longitudinal protein changes in blood plasma associated with the rate of cognitive decline in alzheimer's disease. J Alzheimers Dis. 2016; 49(4): 1105-14, CrossRef.
Yaffe K, Weston A, Graff-Radford NR, Satterfield S, Simonsick EM, Younkin SG, et al. Association of plasma beta-amyloid level and cognitive reserve with subsequent cognitive decline. JAMA. 2011; 305(3): 261-6, CrossRef.
Albani D, Marizzoni M, Ferrari C, Fusco F, Boeri L, Raimondi I, et al. Plasma Abeta42 as biomarker of prodromal Alzheimer's disease progression in patients with amnestic mild cognitive impairment: evidence from the PharmaCog/E-ADNI study. J Alzheimers Dis 2019; 69(1): 37-48, CrossRef.
Yang YH, Huang LC, Hsieh SW, Huang LJ. Dynamic blood concentrations of Aβ1-40 and Aβ1-42 in alzheimer's disease. Front Cell Dev Biol. 2020; 8: 768, CrossRef.
Prasetyo BT, Lumempouw SF, Ramli Y, Herqutanto. Nilai Normal Montreal Cognitive Assesment versi Indonesia (MoCA-Ina). Jakarta: Program Studi Ilmu Bedah Saraf, Fakultas Kedokteran Universitas Indonesia; 2011, article.
Palmqvist S, Insel PS, Stomrud E, Janelidze S, Zetterberg H, Brix B, et al. Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in alzheimer's disease. EMBO Mol Med. 2019; 11(12): e11170, CrossRef.
Figurski MJ, Waligórska T, Toledo J, Vanderstichele H, Korecka M, Lee VM, et al. Alzheimer's disease neuroimaging initiative. Improved protocol for measurement of plasma β-amyloid in longitudinal evaluation of Alzheimer's Disease Neuroimaging Initiative Study patients. Alzheimers Dement. 2012; 8(4): 250-60, CrossRef.
Manafikhi R, Haik MB, Lahdo R, AlQuobaili F. Plasma amyloid β levels in Alzheimer's disease and cognitively normal controls in Syrian population. Med J Islam Repub Iran. 2021; 35: 19, CrossRef.
Di Battista AM, Heinsinger NM, Rebeck GW. Alzheimer's disease genetic risk factor APOE-ε4 also affects normal brain function. Curr Alzheimer Res. 2016; 13(11): 1200-7, CrossRef.
Serrano-Pozo A, Das S, Hyman BT. APOE and alzheimer's disease: Advances in genetics, pathophysiology, and therapeutic approaches. Lancet Neurol. 2021; 20(1): 68-80, CrossRef.
Castellano JM, Kim J, Stewart FR, Jiang H, DeMattos RB, Patterson BW, et al. Human apoE isoforms differentially regulate brain amyloid-β peptide clearance. Sci Transl Med. 2011; 3(89): 89ra57, CrossRef.
DOI: https://doi.org/10.18585/inabj.v16i6.3404
Copyright (c) 2024 The Prodia Education and Research Institute

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Indexed by:





The Prodia Education and Research Institute