Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2017

Open Access 01-12-2017 | Research

Chemically treated plasma Aβ is a potential blood-based biomarker for screening cerebral amyloid deposition

Authors: Jong-Chan Park, Sun-Ho Han, Hyun Jin Cho, Min Soo Byun, Dahyun Yi, Young Min Choe, Seokjo Kang, Eun Sun Jung, Su Jin Won, Eun Hye Kim, Yu Kyeong Kim, Dong Young Lee, Inhee Mook-Jung

Published in: Alzheimer's Research & Therapy | Issue 1/2017

Login to get access

Abstract

Background

Plasma β-amyloid (Aβ) is a potential candidate for an Alzheimer’s disease (AD) biomarker because blood is an easily accessible bio-fluid, which can be collected routinely, and Aβ is one of the major hallmarks of AD pathogenesis in the brain. However, the association between plasma Aβ levels and AD diagnosis is still unclear due to the instability and inaccurate measurements of plasma Aβ levels in the blood of patients with AD. If a consistent value of plasma Aβ from the blood can be obtained, this might help determine whether plasma Aβ is a potential biomarker for AD diagnosis.

Methods

We predicted the brain amyloid deposit by measuring the plasma Aβ levels. This cross-sectional study included 353 participants (215 cognitively normal, 79 with mild cognitive impairment, and 59 with AD dementia) who underwent Pittsburgh-compound B positron emission tomography (PiB-PET) scans. We treated a mixture of protease inhibitors and phosphatase inhibitors (MPP) and detected plasma Aβ42 and Aβ40 (MPP-Aβ42 and MPP-Aβ40) in a stable manner using xMAP technology.

Results

MPP-Aβ40 and MPP-Aβ42/40 (MPP-Aβs) were significantly different between subjects with positive amyloid deposition (PiB+) and those with negative amyloid deposition (PiB–) (P < 0.0001). Furthermore, MPP-Aβ40 (P < 0.0001, r = 0.23) and MPP-Aβ42/40 ratio (P < 0.0001, r = –0.23) showed significant correlation with global PiB deposition (standardized uptake value ratio). In addition, our integrated multivariable (MPP-Aβ42/40, gender, age, and apolipoprotein E genotypes) logistic regression model proposes a new standard for the prediction of cerebral amyloid deposition.

Conclusions

MPP-Aβ might be one of the potential blood biomarkers for the prediction of PiB-PET positivity in the brain.
Appendix
Available only for authorised users
Literature
1.
2.
Song H, Chang YJ, Moon M, Park SK, Tran PT, Hoang VH, Lee J, Mook-Jung I. Inhibition of glutaminyl cyclase ameliorates amyloid pathology in an animal model of Alzheimer's disease via the modulation of gamma-secretase activity. J Alzheimers Dis. 2015;43:797–807.PubMed
3.
Jansen WJ, Ossenkoppele R, Knol DL, Tijms BM, Scheltens P, Verhey FR, Visser PJ, Amyloid Biomarker Study G, Aalten P, Aarsland D, et al. Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA. 2015;313:1924–38.CrossRefPubMedPubMedCentral
4.
Sheng M, Sabatini BL, Sudhof TC. Synapses and Alzheimer’s disease. Cold Spring Harb Perspect Biol. 2012;4:a005777.
5.
6.
Cataldo JK, Prochaska JJ, Glantz SA. Cigarette smoking is a risk factor for Alzheimer's Disease: an analysis controlling for tobacco industry affiliation. J Alzheimers Dis. 2010;19:465–80.PubMedPubMedCentral
7.
Malouf M, Grimley EJ, Areosa SA. Folic acid with or without vitamin B12 for cognition and dementia. Cochrane Database Syst Rev. 2003;4:CD004514.
8.
Pillai JA, Verghese J. Social networks and their role in preventing dementia. Indian J Psychiatry. 2009;51 Suppl 1:S22–8.PubMedPubMedCentral
9.
Skoog I, Gustafson D. Update on hypertension and Alzheimer's disease. Neurol Res. 2006;28:605–11.CrossRefPubMed
10.
Solfrizzi V, Panza F, Frisardi V, Seripa D, Logroscino G, Imbimbo BP, Pilotto A. Diet and Alzheimer's disease risk factors or prevention: the current evidence. Expert Rev Neurother. 2011;11:677–708.CrossRefPubMed
11.
Radak Z, Hart N, Sarga L, Koltai E, Atalay M, Ohno H, Boldogh I. Exercise plays a preventive role against Alzheimer's disease. J Alzheimers Dis. 2010;20:777–83.PubMed
12.
Kang S, Jeong H, Baek JH, Lee SJ, Han SH, Cho HJ, Kim H, Hong HS, Kim YH, Yi EC, et al. PiB-PET imaging-based serum proteome profiles predict mild cognitive impairment and Alzheimer's disease. J Alzheimers Dis. 2016;53:1563–76.CrossRefPubMed
13.
Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, Bergstrom M, Savitcheva I, Huang GF, Estrada S, et al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann Neurol. 2004;55:306–19.CrossRefPubMed
14.
Hampel H, Teipel SJ, Fuchsberger T, Andreasen N, Wiltfang J, Otto M, Shen Y, Dodel R, Du Y, Farlow M, et al. Value of CSF beta-amyloid1-42 and tau as predictors of Alzheimer's disease in patients with mild cognitive impairment. Mol Psychiatry. 2004;9:705–10.PubMed
15.
16.
Bisaccia E, Berger C, DiSpaltro FX, Armus S, Cahill C, Klainer A. Viral-specific immunization in AIDS-related complex by photopheresis. Ann N Y Acad Sci. 1991;636:321–30.CrossRefPubMed
17.
Lewczuk P, Kornhuber J, Vanmechelen E, Peters O, Heuser I, Maier W, Jessen F, Burger K, Hampel H, Frolich L, et al. Amyloid beta peptides in plasma in early diagnosis of Alzheimer's disease: a multicenter study with multiplexing. Exp Neurol. 2010;223:366–70.CrossRefPubMed
18.
Pesaresi M, Lovati C, Bertora P, Mailland E, Galimberti D, Scarpini E, Quadri P, Forloni G, Mariani C. Plasma levels of beta-amyloid (1-42) in Alzheimer's disease and mild cognitive impairment. Neurobiol Aging. 2006;27:904–5.CrossRefPubMed
19.
Graff-Radford NR, Crook JE, Lucas J, Boeve BF, Knopman DS, Ivnik RJ, Smith GE, Younkin LH, Petersen RC, Younkin SG. Association of low plasma Abeta42/Abeta40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease. Arch Neurol. 2007;64:354–62.CrossRefPubMed
20.
Yaffe K, Weston A, Graff-Radford NR, Satterfield S, Simonsick EM, Younkin SG, Younkin LH, Kuller L, Ayonayon HN, Ding J, Harris TB. Association of plasma beta-amyloid level and cognitive reserve with subsequent cognitive decline. JAMA. 2011;305:261–6.CrossRefPubMedPubMedCentral
21.
Blasko I, Jellinger K, Kemmler G, Krampla W, Jungwirth S, Wichart I, Tragl KH, Fischer P. Conversion from cognitive health to mild cognitive impairment and Alzheimer's disease: prediction by plasma amyloid beta 42, medial temporal lobe atrophy and homocysteine. Neurobiol Aging. 2008;29:1–11.CrossRefPubMed
22.
Fukumoto H, Tennis M, Locascio JJ, Hyman BT, Growdon JH, Irizarry MC. Age but not diagnosis is the main predictor of plasma amyloid beta-protein levels. Arch Neurol. 2003;60:958–64.CrossRefPubMed
23.
van Oijen M, Hofman A, Soares HD, Koudstaal PJ, Breteler MM. Plasma Abeta(1-40) and Abeta(1-42) and the risk of dementia: a prospective case-cohort study. Lancet Neurol. 2006;5:655–60.CrossRefPubMed
24.
Han SH, Jung ES, Sohn JH, Hong HJ, Hong HS, Kim JW, Na DL, Kim M, Kim H, Ha HJ, et al. Human serum transthyretin levels correlate inversely with Alzheimer's disease. J Alzheimers Dis. 2011;25:77–84.PubMed
25.
Han SH, Park JC, Mook-Jung I. Amyloid beta-interacting partners in Alzheimer's disease: from accomplices to possible therapeutic targets. Prog Neurobiol. 2016;137:17–38.CrossRefPubMed
26.
Kuo YM, Kokjohn TA, Kalback W, Luehrs D, Galasko DR, Chevallier N, Koo EH, Emmerling MR, Roher AE. Amyloid-beta peptides interact with plasma proteins and erythrocytes: implications for their quantitation in plasma. Biochem Biophys Res Commun. 2000;268:750–6.CrossRefPubMed
27.
Reyes Barcelo AA, Gonzalez-Velasquez FJ, Moss MA. Soluble aggregates of the amyloid-beta peptide are trapped by serum albumin to enhance amyloid-beta activation of endothelial cells. J Biol Eng. 2009;3:5.CrossRefPubMedPubMedCentral
28.
29.
Schwarzman AL, Goldgaber D. Interaction of transthyretin with amyloid beta-protein: binding and inhibition of amyloid formation. Ciba Found Symp. 1996;199:146–60. discussion 160–4.PubMed
30.
31.
Kumar S, Singh S, Hinze D, Josten M, Sahl HG, Siepmann M, Walter J. Phosphorylation of amyloid-beta peptide at serine 8 attenuates its clearance via insulin-degrading and angiotensin-converting enzymes. J Biol Chem. 2012;287:8641–51.CrossRefPubMedPubMedCentral
32.
Hulmes JD, Bethea D, Ho K, Huang S-P, Ricci DL, Opiteck GJ, Hefta SA. An investigation of plasma collection, stabilization, and storage procedures for proteomic analysis of clinical samples. Clin Proteomics. 2004;1:17–31.CrossRef
33.
Ossenkoppele R, Jansen WJ, Rabinovici GD, Knol DL, van der Flier WM, van Berckel BN, Scheltens P, Visser PJ, Amyloid PETSG, Verfaillie SC, et al. Prevalence of amyloid PET positivity in dementia syndromes: a meta-analysis. JAMA. 2015;313:1939–49.CrossRefPubMedPubMedCentral
34.
Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology. 1993;43:2412–4.CrossRefPubMed
35.
Lee DY, Lee KU, Lee JH, Kim KW, Jhoo JH, Kim SY, Yoon JC, Woo SI, Ha J, Woo JI. A normative study of the CERAD neuropsychological assessment battery in the Korean elderly. J Int Neuropsychol Soc. 2004;10:72–81.PubMed
36.
Association AP. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. American Psychiatric Association Washington, DC. 1994;1–866.
37.
McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack Jr CR, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, et al. 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. Alzheimers Dement. 2011;7:263–9.CrossRefPubMedPubMedCentral
38.
Lee JH, Lee KU, Lee DY, Kim KW, Jhoo JH, Kim JH, Lee KH, Kim SY, Han SH, Woo JI. Development of the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet (CERAD-K): clinical and neuropsychological assessment batteries. J Gerontol B Psychol Sci Soc Sci. 2002;57:P47–53.CrossRefPubMed
39.
Piccinin AM, Muniz-Terrera G, Clouston S, Reynolds CA, Thorvaldsson V, Deary IJ, Deeg DJ, Johansson B, Mackinnon A, Spiro 3rd A, et al. Coordinated analysis of age, sex, and education effects on change in MMSE scores. J Gerontol B Psychol Sci Soc Sci. 2013;68:374–90.CrossRefPubMed
40.
41.
Park JC, Baik SH, Han SH, Cho HJ, Choi H, Kim HJ, Choi H, Lee W, Kim DK, Mook-Jung I. Annexin A1 restores Abeta1-42 -induced blood-brain barrier disruption through the inhibition of RhoA-ROCK signaling pathway. Aging Cell. 2017;16:149-61.
42.
Fanali G, di Masi A, Trezza V, Marino M, Fasano M, Ascenzi P. Human serum albumin: from bench to bedside. Mol Aspects Med. 2012;33:209–90.CrossRefPubMed
43.
Jupin M, Michiels PJ, Girard FC, Spraul M, Wijmenga SS. NMR metabolomics profiling of blood plasma mimics shows that medium- and long-chain fatty acids differently release metabolites from human serum albumin. J Magn Reson. 2014;239:34–43.CrossRefPubMed
44.
Rangachari V, Moore BD, Reed DK, Sonoda LK, Bridges AW, Conboy E, Hartigan D, Rosenberry TL. Amyloid-beta(1-42) rapidly forms protofibrils and oligomers by distinct pathways in low concentrations of sodium dodecylsulfate. Biochemistry. 2007;46:12451–62.CrossRefPubMed
45.
46.
Bibl M, Welge V, Esselmann H, Wiltfang J. Stability of amyloid-beta peptides in plasma and serum. Electrophoresis. 2012;33:445–50.CrossRefPubMed
47.
Faurschou M, Borregaard N. Neutrophil granules and secretory vesicles in inflammation. Microbes Infect. 2003;5:1317–27.CrossRefPubMed
48.
Chertov O, Yang D, Howard OM, Oppenheim JJ. Leukocyte granule proteins mobilize innate host defenses and adaptive immune responses. Immunol Rev. 2000;177:68–78.CrossRefPubMed
49.
50.
Boyanton Jr BL, Blick KE. Stability studies of twenty-four analytes in human plasma and serum. Clin Chem. 2002;48:2242–7.PubMed
51.
Baker AH, Edwards DR, Murphy G. Metalloproteinase inhibitors: biological actions and therapeutic opportunities. J Cell Sci. 2002;115:3719–27.CrossRefPubMed
52.
Clark S, Youngman LD, Palmer A, Parish S, Peto R, Collins R. Stability of plasma analytes after delayed separation of whole blood: implications for epidemiological studies. Int J Epidemiol. 2003;32:125–30.CrossRefPubMed
53.
Zimmerman LJ, Li M, Yarbrough WG, Slebos RJ, Liebler DC. Global stability of plasma proteomes for mass spectrometry-based analyses. Mol Cell Proteomics. 2012;11:M111–M014340.CrossRefPubMedPubMedCentral
54.
Vina J, Lloret A. Why women have more Alzheimer's disease than men: gender and mitochondrial toxicity of amyloid-beta peptide. J Alzheimers Dis. 2010;20 Suppl 2:S527–33.PubMed
55.
Chartier-Harlin MC, Parfitt M, Legrain S, Perez-Tur J, Brousseau T, Evans A, Berr C, Vidal O, Roques P, Gourlet V, et al. Apolipoprotein E, epsilon 4 allele as a major risk factor for sporadic early and late-onset forms of Alzheimer's disease: analysis of the 19q13.2 chromosomal region. Hum Mol Genet. 1994;3:569–74.CrossRefPubMed
56.
Assini A, Cammarata S, Vitali A, Colucci M, Giliberto L, Borghi R, Inglese ML, Volpe S, Ratto S, Dagna-Bricarelli F, et al. Plasma levels of amyloid beta-protein 42 are increased in women with mild cognitive impairment. Neurology. 2004;63:828–31.CrossRefPubMed
57.
Lopez OL, Kuller LH, Mehta PD, Becker JT, Gach HM, Sweet RA, Chang YF, Tracy R, DeKosky ST. Plasma amyloid levels and the risk of AD in normal subjects in the Cardiovascular Health Study. Neurology. 2008;70:1664–71.CrossRefPubMedPubMedCentral
Metadata
Title
Chemically treated plasma Aβ is a potential blood-based biomarker for screening cerebral amyloid deposition
Authors
Jong-Chan Park
Sun-Ho Han
Hyun Jin Cho
Min Soo Byun
Dahyun Yi
Young Min Choe
Seokjo Kang
Eun Sun Jung
Su Jin Won
Eun Hye Kim
Yu Kyeong Kim
Dong Young Lee
Inhee Mook-Jung
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2017
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-017-0248-8

Other articles of this Issue 1/2017

Alzheimer's Research & Therapy 1/2017 Go to the issue

Research

Preclinical effects of APOE ε4 on cerebrospinal fluid Aβ42 concentrations

Research

Evaluation of a research diagnostic algorithm for DSM-5 neurocognitive disorders in a population-based cohort of older adults

Research

Antipsychotic prescribing for Alzheimer’s disease and related disorders in specialized settings from 2010 to 2014 in France: a repeated cross-sectional study

Research

Race modifies the relationship between cognition and Alzheimer’s disease cerebrospinal fluid biomarkers

Review

The influence of insulin resistance on cerebrospinal fluid and plasma biomarkers of Alzheimer’s pathology

Research

DHA brain uptake and APOE4 status: a PET study with [1-11C]-DHA