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

Danni Li; Michelle M. Mielke

doi:10.1007/s40120-019-00164-5

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

Danni Li, Michelle M. Mielke

Laboratory Medicine and Pathology

Research output: Contribution to journal › Review article › peer-review

79 Scopus citations

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.

Original language	English (US)
Pages (from-to)	73-82
Number of pages	10
Journal	Neurology and Therapy
Volume	8
DOIs	https://doi.org/10.1007/s40120-019-00164-5
State	Published - Dec 1 2019

Bibliographical note

Funding Information:
Effort for this work was supported by the National Institutes of Health/National Institute on Aging grants U01 AG006786, R01 AG049704, and R01 AG059654. No funding was received for the publication of this article. All named authors meet the International Committee of medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published. Danni Li receives research support from NIH and Center for Disease Control and Prevention. Michelle Mielke served as a consultant to Eli Lilly and receives research support from the National Institutes of Health (NIH), Department of Defense, and unrestricted research grants from Biogen. This article is based on previously conducted studies and does not involve any new studies of human or animal subjects performed by any of the authors. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/ ), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Funding Information:
Effort for this work was supported by the National Institutes of Health/National Institute on Aging grants U01 AG006786, R01 AG049704, and R01 AG059654. No funding was received for the publication of this article.

Funding Information:
Danni Li receives research support from NIH and Center for Disease Control and Prevention. Michelle Mielke served as a consultant to Eli Lilly and receives research support from the National Institutes of Health (NIH), Department of Defense, and unrestricted research grants from Biogen.

Publisher Copyright:
© 2019, The Author(s).

Keywords

Alzheimer’s disease
Amyloid-beta
Blood biomarkers
Neurofilament
Single molecule array technology
Tau

Access

10.1007/s40120-019-00164-5

OpenUrl availability

Full text

Cite this

@article{2e7231ebdd264d7cb8052d93d9041ac5,

title = "An Update on Blood-Based Markers of Alzheimer{\textquoteright}s Disease Using the SiMoA Platform",

abstract = "The development of blood-based biomarkers of Alzheimer{\textquoteright}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.",

keywords = "Alzheimer{\textquoteright}s disease, Amyloid-beta, Blood biomarkers, Neurofilament, Single molecule array technology, Tau",

author = "Danni Li and Mielke, {Michelle M.}",

note = "Funding Information: Effort for this work was supported by the National Institutes of Health/National Institute on Aging grants U01 AG006786, R01 AG049704, and R01 AG059654. No funding was received for the publication of this article. All named authors meet the International Committee of medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published. Danni Li receives research support from NIH and Center for Disease Control and Prevention. Michelle Mielke served as a consultant to Eli Lilly and receives research support from the National Institutes of Health (NIH), Department of Defense, and unrestricted research grants from Biogen. This article is based on previously conducted studies and does not involve any new studies of human or animal subjects performed by any of the authors. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/ ), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Funding Information: Effort for this work was supported by the National Institutes of Health/National Institute on Aging grants U01 AG006786, R01 AG049704, and R01 AG059654. No funding was received for the publication of this article. Funding Information: Danni Li receives research support from NIH and Center for Disease Control and Prevention. Michelle Mielke served as a consultant to Eli Lilly and receives research support from the National Institutes of Health (NIH), Department of Defense, and unrestricted research grants from Biogen. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1007/s40120-019-00164-5",

language = "English (US)",

volume = "8",

pages = "73--82",

journal = "Neurology and Therapy",

issn = "2193-8253",

publisher = "Springer Healthcare",

}

TY - JOUR

T1 - An Update on Blood-Based Markers of Alzheimer’s Disease Using the SiMoA Platform

AU - Li, Danni

AU - Mielke, Michelle M.

N1 - Funding Information: Effort for this work was supported by the National Institutes of Health/National Institute on Aging grants U01 AG006786, R01 AG049704, and R01 AG059654. No funding was received for the publication of this article. All named authors meet the International Committee of medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published. Danni Li receives research support from NIH and Center for Disease Control and Prevention. Michelle Mielke served as a consultant to Eli Lilly and receives research support from the National Institutes of Health (NIH), Department of Defense, and unrestricted research grants from Biogen. This article is based on previously conducted studies and does not involve any new studies of human or animal subjects performed by any of the authors. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/ ), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Funding Information: Effort for this work was supported by the National Institutes of Health/National Institute on Aging grants U01 AG006786, R01 AG049704, and R01 AG059654. No funding was received for the publication of this article. Funding Information: Danni Li receives research support from NIH and Center for Disease Control and Prevention. Michelle Mielke served as a consultant to Eli Lilly and receives research support from the National Institutes of Health (NIH), Department of Defense, and unrestricted research grants from Biogen. Publisher Copyright: © 2019, The Author(s).

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

KW - Alzheimer’s disease

KW - Amyloid-beta

KW - Blood biomarkers

KW - Neurofilament

KW - Single molecule array technology

KW - Tau

UR - http://www.scopus.com/inward/record.url?scp=85076354986&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85076354986&partnerID=8YFLogxK

U2 - 10.1007/s40120-019-00164-5

DO - 10.1007/s40120-019-00164-5

M3 - Review article

C2 - 31833025

AN - SCOPUS:85076354986

SN - 2193-8253

VL - 8

SP - 73

EP - 82

JO - Neurology and Therapy

JF - Neurology and Therapy

ER -

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

Abstract

Bibliographical note

Keywords

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this