nach oben

Alzheimer's Research & Therapy

Erschienen in:

01.04.2013 | Review

Biomarkers for Alzheimer's disease in plasma, serum and blood - conceptual and practical problems

verfasst von: Douglas Galasko, Todd E Golde

Erschienen in: Alzheimer's Research & Therapy | Ausgabe 2/2013

Einloggen, um Zugang zu erhalten

Abstract

Substances produced throughout the body are detectable in the blood, which is the most common biological fluid used in clinical testing. Biomarkers for Alzheimer's disease (AD) have long been sought in the blood, but none has become an established or validated diagnostic test. Companion reviews in Alzheimer's Research & Therapy will review specific types of biomarkers or applications; in this overview, we cover key concepts related to AD blood biomarker studies in general. Reasons for the difficulty of detecting markers of a brain-specific disorder, such as AD, in the blood are outlined; these pose conceptual challenges for blood biomarker discovery and development. Applications of blood tests in AD go beyond screening and diagnostic testing; other potential uses are risk assessment, prognostication, and evaluation of treatment target engagement, toxicity, and outcome. Opportunities and questions that may surround these different uses are discussed. A systematic approach to biomarker discovery, detection, assay development and quality control, sample collection, handling and storage, and design and analysis of clinical studies needs to be implemented at every step of discovery and translation to identify an interpretable and useful biomarker.

Altar CA, Amakye D, Bounos D, Bloom J, Clack G, Dean R, Devanarayan V, Fu D, Furlong S, Hinman L, Girman C, Lathia C, Lesko L, Madani S, Mayne J, Meyer J, Raunig D, Sager P, Williams SA, Wong P, Zerba K: A prototypical process for creating evidentiary standards for biomarkers and diagnostics. Clin Pharmacol Therapeutics. 2008, 83: 368-371. 10.1038/sj.clpt.6100451.CrossRef

US Food and Drug Administration approval of amyloid imaging. [http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202008s000lbl.pdf]

Jack CR, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ: Hypothetical model of dynamic biomarkers of the Alzheimer's disease pathological cascade. Lancet Neurol. 2010, 9: 119-128. 10.1016/S1474-4422(09)70299-6.PubMedCentralCrossRefPubMed

Koyama A, Okerere OI, Yang T, Blacker D, Selkoe DJ, Grodstein F: Plasma amyloid-β as a predictor of dementia and cognitive decline: a systematic review. Arch Neurol. 2012, 69: 824-831. 10.1001/archneurol.2011.1841.PubMedCentralCrossRefPubMed

Ray S, Britschgi M, Hergbert C, Takeda-Uchimura Y, Boxer A, Blennow K, Friedman LF, Galasko DR, Jutel M, Karydas A, Kaye JA, Leszek J, Miller BL, Minthon L, Quinn JF, Rabinovici GD, Robinson WH, Sabbagh MN, So YT, Sparks DL, Tabaton M, Tinklenberg J, Yesavage JA, Tibshirami R, Wyss-Coray T: Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins. Nat Med. 2007, 13: 1359-1362. 10.1038/nm1653.CrossRefPubMed

Soares HD, Potter WZ, Pickering E, Kuhn M, Immermann FW, Shera DM, Ferm M, Dean RA, Simon AJ, Swenson F, Siuciak JA, Kaplow J, Thambisetty M, Zagouras P, Koroshetz WJ, Wan HI, Trojanowski JQ, Shaw LM, for the Biomarkers Consortium Alzheimer's Disease Plasma Proteomics Project: Plasma biomarkers associated with the apolipoprotein E genotype and Alzheimer disease. Arch Neurol. 2012, 69: 1310-1317.PubMedCentralCrossRefPubMed

Doecke JD, Laws SM, Faux NG, Wilson W, Burnham SC, Lam CP, Mondal A, Bedo J, Bush AI, Brown B, De Ruyck K, Ellis KA, Fowler C, Gupta VB, Head R, Macaulay SL, Pertile K, Rowe CC, Rembach A, Rodrigues M, Rumble R, Szoeke C, Taddei K, Taddei T, Trounson B, Ames D, Masters CL, Martins RN, for the Alzheimer's Disease Neuroimaging Initiative and Australian Imaging Biomarker and Lifestyle Research Group: Blood-based protein biomarkers for diagnosis of Alzheimer disease. Arch Neurol. 2012, 69: 1318-1325.CrossRefPubMed

O'Bryant SE, Xiao G, Barber R, Huebinger R, Wilhelmsen K, Edwards M, Graff-Radford N, Doody R, Diaz-Arrastia R, Texas Alzheimer's Research & Care Consortium; Alzheimer's Disease Neuroimaging Initiative: A blood-based screening tool for Alzheimer's disease that spans serum and plasma: findings from TARC and ADNI. PLoS One. 2011, 6: e28092-10.1371/journal.pone.0028092.PubMedCentralCrossRefPubMed

Hu WT, Holtzman DM, Fagan AM, Shaw LM, Perrin R, Arnold SE, Grossman M, Xiong C, Craig-Schapiro R, Clark CM, Pickering E, Kuhn M, Chen Y, Van Deerlin VM, McCluskey L, Elman L, Karlawish J, Chen-Plotkin A, Hurtig HI, Siderowf A, Swenson F, Lee VM, Morris JC, Trojanowski JQ, Soares H, Alzheimer's Disease Neuroimaging Initiative: Plasma multianalyte profiling in mild cognitive impairment and Alzheimer disease. Neurology. 2012, 79: 906-914. 10.1212/WNL.0b013e318266fc51.CrossRef

10.

Johnstone D, Milward EA, Berretta R, Moscato P, Alzheimer's Disease Neuroimaging Initiative: Multivariate protein signatures of pre-clinical Alzheimer's disease in the Alzheimer's disease neuroimaging initiative (ADNI) plasma proteome dataset. PLoS One. 2012, 7: e34341-10.1371/journal.pone.0034341.PubMedCentralCrossRefPubMed

11.

Mehta PD, Pirttila T, Patrick BA, Barshatzky M, Mehta SP: Amyloid beta protein 1-40 and 1-42 levels in matched cerebrospinal fluid and plasma from patients with Alzheimer disease. Neurosci Lett. 2001, 304: 102-106. 10.1016/S0304-3940(01)01754-2.CrossRefPubMed

12.

Fagan AM, Head D, Shah AR, Marcus D, Mintun M, Morris JC, Holtzman DM: Decreased cerebrospinal fluid Abeta(42) correlates with brain atrophy in cognitively normal elderly. Ann Neurol. 2009, 65: 176-183. 10.1002/ana.21559.PubMedCentralCrossRefPubMed

13.

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: 655-660. 10.1016/S1474-4422(06)70501-4.CrossRefPubMed

14.

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: 354-362. 10.1001/archneur.64.3.354.CrossRefPubMed

15.

Lambert JC, Schraen-Maschke S, Richard F, Fievet N, Rouaud O, Berr C, Dartigues JF, Tzourio C, Alpérovitch A, Buée L, Amouyel P: Association of plasma amyloid beta with risk of dementia: the prospective Three-City Study. Neurology. 2009, 73: 847-853. 10.1212/WNL.0b013e3181b78448.CrossRefPubMed

16.

Moore BD, Chakrabarty P, Levites Y, Kukar TL, Baine AM, Moroni T, Ladd TB, Das P, Dickson DW, Golde TE: Overlapping profiles of Abeta peptides in the Alzheimer's disease and pathological aging brains. Alzheimers Res Ther. 2012, 4: 18-10.1186/alzrt121.PubMedCentralCrossRefPubMed

17.

Schrijvers EM, Koudstaal PJ, Hofman A, Breteler MM: Plasma clusterin and the risk of Alzheimer disease. JAMA. 2011, 305: 1322-1326. 10.1001/jama.2011.381.CrossRefPubMed

18.

Schürmann B, Wiese B, Bickel H, Weyerer S, Riedel-Heller SG, Pentzek M, Bachmann C, Williams J, van den Bussche H, Maier W, Jessen F: Association of the Alzheimer's disease clusterin risk allele with plasma clusterin concentration. J Alzheimers Dis. 2011, 25: 421-424.PubMed

19.

Butterfield LH, Potter DM, Kirkwood JM: Multiplex serum biomarker assessments:technical and biostatistical issues. J Translational Med. 2011, 9: 173-186. 10.1186/1479-5876-9-173.CrossRef

20.

Yi J, Craft D, Gelfand CA: Minimizing preanalytical variation of plasma samples by proper blood collection and handling. Methods Mol Biol. 2011, 728: 137-149. 10.1007/978-1-61779-068-3_8.CrossRefPubMed

21.

Lista S, Faltraco F, Hampel H: Biological and methodological challenges of blood-based proteomics in the field of neurological research. Prog Neurobiol. 2013, 101-102: 18-34.CrossRefPubMed

22.

Rifai M, Gillette MA, Carr SA: Protein biomarker discovery and validation: the long and uncertain path to clinical utility. Nat Biotech. 2006, 24: 971-983. 10.1038/nbt1235.CrossRef

23.

Lachno DR, Emerson JK, Vanderstichele H, Gonzales C, Martényi F, Konrad RJ, Talbot JA, Lowe SL, Oefinger PE, Dean RA: Validation of a multiplex assay for simultaneous quantification of amyloid-β peptide species in human plasma with utility for measurements in studies of Alzheimer's disease therapeutics. J Alzheimers Dis. 2012, 32: 905-918.PubMed

24.

van der Burg SH, Kalos M, Gouttefangeas C, Janetzki S, Ottensmeier C, Welters MJ, Romero P, Britten CM, Hoos A: Harmonization of immune biomarker assays for clinical studies. Sci Transl Med. 2011, 3: 108ps44-10.1126/scitranslmed.3002785.CrossRefPubMed

25.

STARDdem homepage. [http://www.starddem.org/]

Titel: Biomarkers for Alzheimer's disease in plasma, serum and blood - conceptual and practical problems
verfasst von: Douglas Galasko
Todd E Golde
Publikationsdatum: 01.04.2013
Verlag: BioMed Central
Erschienen in: Alzheimer's Research & Therapy / Ausgabe 2/2013
Elektronische ISSN: 1758-9193
DOI: https://doi.org/10.1186/alzrt164

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Demenzkranke durch Antipsychotika vielfach gefährdet

Demenz Nachrichten

Der Einsatz von Antipsychotika gegen psychische und Verhaltenssymptome in Zusammenhang mit Demenzerkrankungen erfordert eine sorgfältige Nutzen-Risiken-Abwägung. Neuen Erkenntnissen zufolge sind auf der Risikoseite weitere schwerwiegende Ereignisse zu berücksichtigen.

Nicht Creutzfeldt Jakob, sondern Abführtee-Vergiftung

29.05.2024 Hyponatriämie Nachrichten

Eine ältere Frau trinkt regelmäßig Sennesblättertee gegen ihre Verstopfung. Der scheint plötzlich gut zu wirken. Auf Durchfall und Erbrechen folgt allerdings eine Hyponatriämie. Nach deren Korrektur kommt es plötzlich zu progredienten Kognitions- und Verhaltensstörungen.

Schutz der Synapsen bei Alzheimer

29.05.2024 Morbus Alzheimer Nachrichten

Mit einem Neurotrophin-Rezeptor-Modulator lässt sich möglicherweise eine bestehende Alzheimerdemenz etwas abschwächen: Erste Phase-2-Daten deuten auf einen verbesserten Synapsenschutz.

Sozialer Aufstieg verringert Demenzgefahr

24.05.2024 Demenz Nachrichten

Ein hohes soziales Niveau ist mit die beste Versicherung gegen eine Demenz. Noch geringer ist das Demenzrisiko für Menschen, die sozial aufsteigen: Sie gewinnen fast zwei demenzfreie Lebensjahre. Umgekehrt steigt die Demenzgefahr beim sozialen Abstieg.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2013

Plasma tau levels in Alzheimer's disease

Targeting norepinephrine in mild cognitive impairment and Alzheimer's disease

Modeling the heterogeneity in risk of progression to Alzheimer's disease acrosscognitive profiles in mild cognitive impairment

5-HT6 receptors and Alzheimer's disease

Have we learnt all we need to know from genetic studies - is genetics over in Alzheimer's disease?

Plasma amyloid beta measurements - a desired but elusive Alzheimer's disease biomarker