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
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Neurology and Therapy
Published in: Neurology and Therapy 2/2019

Open Access 01-12-2019 | Alzheimer's Disease | Review

An Update on Blood-Based Markers of Alzheimer’s Disease Using the SiMoA Platform

Authors: Danni Li, Michelle M. Mielke

Published in: Neurology and Therapy | Special Issue 2/2019

Login to get access

Abstract

The development of blood-based biomarkers of Alzheimer’s disease (AD) pathology as tools for screening the general population, and as the first step in a multistep process to determine which non-demented individuals are at greatest risk of developing AD dementia, is essential. Proteins that are reflective of AD pathology, such as amyloid beta 42 (Aβ42), tau proteins [total tau (T-tau) and phosphorylated tau (P-tau)], and neurofilament light chain (NfL), are detectable in the blood. However, a major challenge in measuring these blood-based proteins is that their concentrations are much lower in plasma or serum than in the cerebrospinal fluid. Single molecule array (SiMoA) is an ultrasensitive technology that can detect proteins in blood at sub-femtomolar concentrations (i.e., 10−16 M). In this review, we focus on the utility of SiMoA assays for the measurement of plasma or serum Aβ42, P-tau, T-tau, and NfL levels and discuss future directions.
Literature
1.
Jack CR Jr, Bennett DA, Blennow K, et al. NIA-AA Research Framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14(4):535–62.PubMedCrossRef
2.
Blennow K, Hampel H. CSF markers for incipient Alzheimer’s disease. Lancet Neurol. 2003;2(10):605–13.PubMedCrossRef
3.
O’Bryant SE, Mielke MM, Rissman RA, et al. Blood-based biomarkers in Alzheimer disease: current state of the science and a novel collaborative paradigm for advancing from discovery to clinic. Alzheimers Dement. 2017;13(1):45–58.PubMedCrossRef
4.
5.
6.
Kuo YM, Emmerling MR, Lampert HC, et al. High levels of circulating Abeta42 are sequestered by plasma proteins in Alzheimer’s disease. Biochem Biophys Res Commun. 1999;257(3):787–91.PubMedCrossRef
7.
Kuo YM, Kokjohn TA, Kalback W, et al. Amyloid-beta peptides interact with plasma proteins and erythrocytes: implications for their quantitation in plasma. Biochem Biophys Res Commun. 2000;268(3):750–6.PubMedCrossRef
8.
Ono K, Noguchi-Shinohara M, Samuraki M, et al. Blood-borne factors inhibit Alzheimer’s beta-amyloid fibril formation in vitro. Exp Neurol. 2006;202(1):125–32.PubMedCrossRef
9.
Biere AL, Ostaszewski B, Stimson ER, Hyman BT, Maggio JE, Selkoe DJ. Amyloid beta-peptide is transported on lipoproteins and albumin in human plasma. J Biol Chem. 1996;271(51):32916–22.PubMedCrossRef
10.
Rissin DM, Kan CW, Campbell TG, et al. Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations. Nat Biotechnol. 2010;28(6):595–9.PubMedPubMedCentralCrossRef
11.
Ovod V, Ramsey KN, Mawuenyega KG, et al. Amyloid beta concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis. Alzheimers Dement. 2017;13(8):841–9.PubMedCrossRef
12.
Nakamura A, Kaneko N, Villemagne VL, et al. High performance plasma amyloid-beta biomarkers for Alzheimer’s disease. Nature. 2018;554(7691):249–54.PubMedCrossRef
13.
Yang SY, Chiu MJ, Chen TF, Horng HE. Detection of plasma biomarkers using immunomagnetic reduction: a promising method for the early diagnosis of Alzheimer’s disease. Neurol Ther. 2017;6[Suppl 1]:37–56.PubMedPubMedCentralCrossRef
14.
Kim Y, Yoo YK, Kim HY, et al. Comparative analyses of plasma amyloid-beta levels in heterogeneous and monomerized states by interdigitated microelectrode sensor system. Sci Adv. 2019;5(4):eaav1388.PubMedPubMedCentralCrossRef
15.
Wilson DH, Rissin DM, Kan CW, et al. The Simoa HD-1 analyzer: a novel fully automated digital immunoassay analyzer with single-molecule sensitivity and multiplexing. J Lab Autom. 2016;21(4):533–47.PubMedCrossRef
16.
Kaneko N, Yamamoto R, Sato TA, Tanaka K. Identification and quantification of amyloid beta-related peptides in human plasma using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Proc Jpn Acad Ser B Phys Biol Sci. 2014;90(3):104–17.PubMedPubMedCentralCrossRef
17.
18.
Lue LF, Guerra A, Walker DG. Amyloid beta and tau as Alzheimer’s disease blood biomarkers: promise from new technologies. Neurol Ther. 2017;6[Suppl 1]:25–36.PubMedPubMedCentralCrossRef
19.
Keshavan A, Heslegrave A, Zetterberg H, Schott JM. Stability of blood-based biomarkers of Alzheimer’s disease over multiple freeze–thaw cycles. Alzheimers Dement (Amst). 2018;10:448–51.PubMedPubMedCentralCrossRef
20.
Verberk IMW, Slot RE, Verfaillie SCJ, et al. Plasma amyloid as prescreener for the earliest Alzheimer pathological changes. Ann Neurol. 2018;84(5):648–58.PubMedPubMedCentralCrossRef
21.
Vergallo A, Megret L, Lista S, et al. Plasma amyloid beta 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer’s disease. Alzheimers Dement. 2019;15(6):764–75.PubMedCrossRef
22.
Palmqvist S, Insel PS, Zetterberg H, et al. Accurate risk estimation of beta-amyloid positivity to identify prodromal Alzheimer’s disease: cross-validation study of practical algorithms. Alzheimers Dement. 2019;15(2):194–204.PubMedCrossRef
23.
Teunissen CE, Chiu MJ, Yang CC, et al. Plasma amyloid-beta (Abeta42) correlates with cerebrospinal fluid Abeta42 in Alzheimer’s disease. J Alzheimers Dis. 2018;62(4):1857–63.PubMedCrossRef
24.
Olsson B, Lautner R, Andreasson U, et al. CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol. 2016;15(7):673–84.PubMedCrossRef
25.
Palmqvist S, Zetterberg H, Mattsson N, et al. Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease. Neurology. 2015;85(14):1240–9.PubMedPubMedCentralCrossRef
26.
Hesse C, Rosengren L, Andreasen N, et al. Transient increase in total tau but not phospho-tau in human cerebrospinal fluid after acute stroke. Neurosci Lett. 2001;297(3):187–90.PubMedCrossRef
27.
Ost M, Nylen K, Csajbok L, et al. Initial CSF total tau correlates with 1-year outcome in patients with traumatic brain injury. Neurology. 2006;67(9):1600–4.PubMedCrossRef
28.
Skillback T, Rosen C, Asztely F, Mattsson N, Blennow K, Zetterberg H. Diagnostic performance of cerebrospinal fluid total tau and phosphorylated tau in Creutzfeldt–Jakob disease: results from the Swedish Mortality Registry. JAMA Neurol. 2014;71(4):476–83.PubMedCrossRef
29.
Buerger K, Otto M, Teipel SJ, et al. Dissociation between CSF total tau and tau protein phosphorylated at threonine 231 in Creutzfeldt–Jakob disease. Neurobiol Aging. 2006;27(1):10–5.PubMedCrossRef
30.
Tatebe H, Kasai T, Ohmichi T, et al. Quantification of plasma phosphorylated tau to use as a biomarker for brain Alzheimer pathology: pilot case–control studies including patients with Alzheimer’s disease and down syndrome. Mol Neurodegener. 2017;12(1):63.PubMedPubMedCentralCrossRef
31.
Park JC, Han SH, Yi D, et al. Plasma tau/amyloid-beta1-42 ratio predicts brain tau deposition and neurodegeneration in Alzheimer’s disease. Brain. 2019;142(3):771–86.PubMedCrossRef
32.
Mielke MM, Hagen CE, Xu J, et al. Plasma phospho-tau181 increases with Alzheimer’s disease clinical severity and is associated with tau- and amyloid-positron emission tomography. Alzheimers Dement. 2018;14(8):989–97.PubMedCrossRef
33.
Chen Z, Mengel D, Keshavan A, et al. Learnings about the complexity of extracellular tau aid development of a blood-based screen for Alzheimer’s disease. Alzheimers Dement. 2019;15(3):487–96.PubMedCrossRef
34.
35.
Pase MP, Beiser AS, Himali JJ, et al. Assessment of plasma total tau level as a predictive biomarker for dementia and related endophenotypes. JAMA Neurol. 2019;76(5):598–606.PubMedPubMedCentralCrossRef
36.
Deters KD, Risacher SL, Kim S, et al. Plasma tau association with brain atrophy in mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis. 2017;58(4):1245–54.PubMedPubMedCentralCrossRef
37.
Dage JL, Wennberg AM, Airey DC, et al. Levels of tau protein in plasma are associated with neurodegeneration and cognitive function in a population-based elderly cohort. Alzheimers Dement. 2016;12(12):1226–34.PubMedCrossRef
38.
Mielke MM, Hagen CE, Wennberg AMV, et al. Association of plasma total tau level with cognitive decline and risk of mild cognitive impairment or dementia in the Mayo Clinic Study on Aging. JAMA Neurol. 2017;74(9):1073–80.PubMedPubMedCentralCrossRef
39.
Hoffman PN, Cleveland DW, Griffin JW, Landes PW, Cowan NJ, Price DL. Neurofilament gene expression: a major determinant of axonal caliber. Proc Natl Acad Sci USA. 1987;84(10):3472–6.PubMedPubMedCentralCrossRef
40.
Norgren N, Rosengren L, Stigbrand T. Elevated neurofilament levels in neurological diseases. Brain Res. 2003;987(1):25–31.PubMedCrossRef
41.
Khalil M, Teunissen CE, Otto M, et al. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol. 2018;14(10):577–89.PubMedCrossRef
42.
Mielke MM, Syrjanen JA, Blennow K, et al. Plasma and CSF neurofilament light: relation to longitudinal neuroimaging and cognitive measures. Neurology. 2019;93(3):e252–60.PubMedPubMedCentralCrossRef
43.
Disanto G, Barro C, Benkert P, et al. Serum neurofilament light: a biomarker of neuronal damage in multiple sclerosis. Ann Neurol. 2017;81(6):857–70.PubMedPubMedCentralCrossRef
44.
Gaetani L, Blennow K, Calabresi P, Di Filippo M, Parnetti L, Zetterberg H. Neurofilament light chain as a biomarker in neurological disorders. J Neurol Neurosurg Psychiatry. 2019;90(8):870–81.PubMedCrossRef
45.
Lewczuk P, Ermann N, Andreasson U, et al. Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease. Alzheimers Res Ther. 2018;10(1):71.PubMedPubMedCentralCrossRef
46.
Scherling CS, Hall T, Berisha F, et al. Cerebrospinal fluid neurofilament concentration reflects disease severity in frontotemporal degeneration. Ann Neurol. 2014;75(1):116–26.PubMedPubMedCentralCrossRef
47.
Teunissen CE, Dijkstra C, Polman C. Biological markers in CSF and blood for axonal degeneration in multiple sclerosis. Lancet Neurol. 2005;4(1):32–41.PubMedCrossRef
48.
49.
Hansson O, Janelidze S, Hall S, et al. Blood-based NfL: a biomarker for differential diagnosis of parkinsonian disorder. Neurology. 2017;88(10):930–7.PubMedPubMedCentralCrossRef
50.
Mattsson N, Andreasson U, Zetterberg H, Blennow K. Association of plasma neurofilament light with neurodegeneration in patients with Alzheimer disease. JAMA Neurol. 2017;74(5):557–66.PubMedPubMedCentralCrossRef
51.
Preische O, Schultz SA, Apel A, et al. Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease. Nat Med. 2019;25(2):277–83.PubMedPubMedCentralCrossRef
52.
Mattsson N, Cullen NC, Andreasson U, Zetterberg H, Blennow K. Association between longitudinal plasma neurofilament light and neurodegeneration in patients with Alzheimer disease. JAMA Neurol. 2019;76(7):791–9.PubMedPubMedCentralCrossRef
53.
Metadata
Title
An Update on Blood-Based Markers of Alzheimer’s Disease Using the SiMoA Platform
Authors
Danni Li
Michelle M. Mielke
Publication date
01-12-2019
Publisher
Springer Healthcare
Published in
Neurology and Therapy / Issue Special Issue 2/2019
Print ISSN: 2193-8253
Electronic ISSN: 2193-6536
DOI
https://doi.org/10.1007/s40120-019-00164-5

Other articles of this Special Issue 2/2019

Neurology and Therapy 2/2019 Go to the issue

Review

Reflections on the Utility of the Retina as a Biomarker for Alzheimer’s Disease: A Literature Review

Review

Neurophysiological Markers of Alzheimer’s Disease: Quantitative EEG Approach

Editorial

Peripheral Biomarkers for Alzheimer’s Disease: Update and Progress

Review

Salivary Biomarkers for Alzheimer’s Disease and Related Disorders

Review

Advance in Plasma AD Core Biomarker Development: Current Findings from Immunomagnetic Reduction-Based SQUID Technology

Review

A Review on MS-Based Blood Biomarkers for Alzheimer’s Disease