For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
38
views
157
references
 Top references
cited by
86
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      219
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Blood‐based biomarkers for Alzheimer's disease

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Neurodegenerative disorders such as Alzheimer's disease (AD) represent a mounting public health challenge. As these diseases are difficult to diagnose clinically, biomarkers of underlying pathophysiology are playing an ever‐increasing role in research, clinical trials, and in the clinical work‐up of patients. Though cerebrospinal fluid (CSF) and positron emission tomography (PET)‐based measures are available, their use is not widespread due to limitations, including high costs and perceived invasiveness. As a result of rapid advances in the development of ultra‐sensitive assays, the levels of pathological brain‐ and AD‐related proteins can now be measured in blood, with recent work showing promising results. Plasma P‐tau appears to be the best candidate marker during symptomatic AD (i.e., prodromal AD and AD dementia) and preclinical AD when combined with Aβ42/Aβ40. Though not AD‐specific, blood NfL appears promising for the detection of neurodegeneration and could potentially be used to detect the effects of disease‐modifying therapies. This review provides an overview of the progress achieved thus far using AD blood‐based biomarkers, highlighting key areas of application and unmet challenges.

          Abstract

          This Review discusses recent advances in blood‐based biomarkers for Alzheimer's disease, highlighting the key areas of application and unmet challenges.

          Related collections

          Most cited references157

          • Record: found
          • Abstract: found
          • Article: found

          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

          Guy M McKhann, David S. Knopman, Howard Chertkow … (2011)
          The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia. Copyright © 2011. Published by Elsevier Inc.
          Article 0 comments Cited 3075 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease

            Clifford R. Jack, David Bennett, Kaj Blennow … (2018)
            In 2011, the National Institute on Aging and Alzheimer’s Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer’s disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer’s Association to update and unify the 2011 guidelines. This unifying update is labeled a “research framework” because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer’s Association Research Framework, Alzheimer’s disease (AD) is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct. The research framework focuses on the diagnosis of AD with biomarkers in living persons. Biomarkers are grouped into those of β amyloid deposition, pathologic tau, and neurodegeneration [AT(N)]. This ATN classification system groups different biomarkers (imaging and biofluids) by the pathologic process each measures. The AT(N) system is flexible in that new biomarkers can be added to the three existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when they become available. We focus on AD as a continuum, and cognitive staging may be accomplished using continuous measures. However, we also outline two different categorical cognitive schemes for staging the severity of cognitive impairment: a scheme using three traditional syndromal categories and a six-stage numeric scheme. It is important to stress that this framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms. We appreciate the concern that this biomarker-based research framework has the potential to be misused. Therefore, we emphasize, first, it is premature and inappropriate to use this research framework in general medical practice. Second, this research framework should not be used to restrict alternative approaches to hypothesis testing that do not use biomarkers. There will be situations where biomarkers are not available or requiring them would be counterproductive to the specific research goals (discussed in more detail later in the document). Thus, biomarker-based research should not be considered a template for all research into age-related cognitive impairment and dementia; rather, it should be applied when it is fit for the purpose of the specific research goals of a study. Importantly, this framework should be examined in diverse populations. Although it is possible that β-amyloid plaques and neurofibrillary tau deposits are not causal in AD pathogenesis, it is these abnormal protein deposits that define AD as a unique neurodegenerative disease among different disorders that can lead to dementia. We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia. This approach also will enable a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people.
            Article 0 comments Cited 2952 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found

              The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

              Marilyn Albert, Steven Dekosky, Dennis D Dickson … (2011)
              The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of developing criteria for the symptomatic predementia phase of Alzheimer's disease (AD), referred to in this article as mild cognitive impairment due to AD. The workgroup developed the following two sets of criteria: (1) core clinical criteria that could be used by healthcare providers without access to advanced imaging techniques or cerebrospinal fluid analysis, and (2) research criteria that could be used in clinical research settings, including clinical trials. The second set of criteria incorporate the use of biomarkers based on imaging and cerebrospinal fluid measures. The final set of criteria for mild cognitive impairment due to AD has four levels of certainty, depending on the presence and nature of the biomarker findings. Considerable work is needed to validate the criteria that use biomarkers and to standardize biomarker analysis for use in community settings. Copyright © 2011 The Alzheimer's Association. All rights reserved.
              Article 0 comments Cited 1948 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Antoine Leuzy:
                ORCID: https://orcid.org/0000-0003-4542-7879
                antoine.leuzy@med.lu.se
                Oskar Hansson:
                ORCID: https://orcid.org/0000-0001-8467-7286
                oskar.hansson@med.lu.se
                Journal
                Journal ID (nlm-ta): EMBO Mol Med
                Journal ID (iso-abbrev): EMBO Mol Med
                Journal ID (doi): 10.1002/(ISSN)1757-4684
                Journal ID (publisher-id): EMMM
                Journal ID (hwp): embomm
                Title: EMBO Molecular Medicine
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 1757-4676
                ISSN (Electronic): 1757-4684
                Publication date (Electronic): 03 December 2021
                Publication date (Print): 11 January 2022
                Volume: 14
                Issue: 1 ( doiID: 10.1002/emmm.v14.1 )
                Electronic Location Identifier: e14408
                Affiliations
                [ 1 ] Clinical Memory Research Unit Department of Clinical Sciences Lund University Malmö Sweden
                [ 2 ] Department of Neurology Skåne University Hospital Lund Sweden
                [ 3 ] Wallenberg Centre for Molecular Medicine Lund University Lund Sweden
                [ 4 ] Memory Clinic Skåne University Hospital Lund Sweden
                [ 5 ] Stark Neuroscience Research Institute Indiana University School of Medicine Indianapolis IN USA
                Author notes
                [*] [* ] Corresponding author. Tel: +46 (0)222 0660; E‐mail: antoine.leuzy@ 123456med.lu.se

                Corresponding author. Tel: +46 (0)40 331000; E‐mail: oskar.hansson@ 123456med.lu.se

                Author information
                https://orcid.org/0000-0003-4542-7879
                https://orcid.org/0000-0002-8885-7724
                https://orcid.org/0000-0002-9267-1930
                https://orcid.org/0000-0003-2869-8378
                https://orcid.org/0000-0002-2192-1699
                https://orcid.org/0000-0001-8467-7286
                Article
                Publisher ID: EMMM202114408
                DOI: 10.15252/emmm.202114408
                PMC ID: 8749476
                PubMed ID: 34859598
                SO-VID: 2b98121b-44d2-4d4c-9ffa-47a7ef80fb8a
                Copyright © © 2021 The Authors. Published under the terms of the CC BY 4.0 license
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date revision received : 02 November 2021
                Date received : 08 April 2021
                Date accepted : 05 November 2021
                Page count
                Figures: 3, Tables: 0, Pages: 15, Words: 14291
                Funding
                Funded by: Swedish Research Council
                Award ID: 2016‐00906
                Funded by: Knut and Alice Wallenberg foundation
                Award ID: 2017‐0383
                Funded by: Marianne and Marcus Wallenberg foundation
                Award ID: 2015.0125
                Funded by: Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson’s disease) at Lund University
                Funded by: Swedish Alzheimer Foundation
                Award ID: AF‐939932
                Funded by: Swedish Brain Foundation
                Award ID: FO2021‐0293
                Funded by: Parkinson foundation of Sweden
                Award ID: 1280/20
                Funded by: Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse
                Funded by: Skåne University Hospital Foundation
                Award ID: 2020‐O000028
                Funded by: Regionalt Forskningsstöd
                Award ID: 2020‐0314
                Funded by: Swedish federal government under the ALF agreement
                Award ID: 2018‐Projekt0279
                Categories
                Subject: Review
                Subject: Reviews
                Custom metadata
                source-schema-version-number 2.0
                cover-date 11 January 2022
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.7.0 mode:remove_FC converted:11.01.2022

                ScienceOpen disciplines: Molecular medicine
                Keywords: alzheimer,aβ,biomarkers,blood,p‐tau,neuroscience
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: alzheimer, aβ, biomarkers, blood, p‐tau, neuroscience

                Comments

                Comment on this article

                scite_

                Similar content219

                See all similar

                Cited by84

                See all cited by

                Most referenced authors2,929

                See all reference authors