Comparison of Plasma p-tau217 and [ <sup>18</sup>F]FDG-PET for Identifying Alzheimer Disease in People With Early-Onset or Atypical Dementia

Quispialaya, Kely Mónica; Therriault, Joseph; Aliaga, Antonio; Benedet, Andréa L.; Ashton, Nicholas J.; Karikari, Thomas K.; Cassa Macedo, Arthur; Rahmouni, Nesrine; Tissot, Cécile; Fernandez Arias, Jaime; Wang, Yi-Ting Tina; Trudel, Lydia; Hosseini, Seyyed Ali Asghar; Matsudaira, Takashi; Chan, Tevy; Pascoal, Tharick Ali; Gilfix, Brian Mark; Vitali, Paolo; Zimmer, Eduardo R.; Provost, Karine; Soucy, Jean-Paul; Gauthier, Serge; Zetterberg, Henrik; Jean-Claude, Bertrand J.; Blennow, Kaj; Rosa-Neto, Pedro

doi:10.1212/WNL.0000000000210211

ScienceOpen: research and publishing network

For Publishers

For Researchers

Blog
About

Search
Advanced search

views

recommends

Record: found
Abstract: found
Article: found

Is Open Access

Comparison of Plasma p-tau217 and [ ¹⁸F]FDG-PET for Identifying Alzheimer Disease in People With Early-Onset or Atypical Dementia

research-article

Author(s): Kely Monica Quispialaya ¹ ^, ² ^, ³ , Joseph Therriault ¹ ^, ³ ^, ⁴ , Antonio Aliaga ² ^, ¹ ^, ⁵ , Andrea L. Benedet ⁶ , Nicholas J. Ashton ⁶ ^, ⁷ , Thomas Karikari ⁶ ^, ⁸ , Arthur Cassa Macedo ¹ ^, ³ ^, ⁴ , Nesrine Rahmouni ¹ ^, ³ ^, ⁴ , Cécile Tissot ¹ ^, ⁴ ^, ⁹ , Jaime Fernandez Arias ¹ ^, ³ ^, ⁴ , Yi-Ting Tina Wang ¹ ^, ⁴ ^, ³ , Lydia Trudel ¹ ^, ³ ^, ⁴ , Seyyed Ali Hosseini ¹ ^, ³ ^, ⁴ , Takashi Matsudaira ¹⁰ ^, ¹¹ , Tevy Chan ¹ ^, ² ^, ³ , Tharick Pascoal ⁸ , Brian Gilfix ¹² , Paolo Vitali ¹ , Eduardo R. Zimmer ¹ ^, ⁵ ^, ¹³ ^, ¹⁴ , Karine Provost ¹⁵ , Jean-Paul Soucy ³ ^, ¹⁵ , Serge Gauthier ¹ ^, ⁴ ^, ¹⁶ , Henrik Zetterberg ⁶ ^, ¹⁷ ^, ¹⁸ ^, ¹⁹ ^, ²⁰ ^, ²¹ , Bertrand J. Jean-Claude ² , Kaj Blennow ⁶ ^, ¹⁷ , Pedro Rosa-Neto ¹ ^, ² ^, ³ ^, ⁴ ^, ¹⁶ ^,

Publication date (Electronic): 23 December 2024

Journal: Neurology

Publisher: Lippincott Williams & Wilkins

Read this article at

ScienceOpen Publisher PMC

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

Background and Objectives

To compare the diagnostic performance of an immunoassay for plasma concentrations of phosphorylated tau (p-tau) 217 with visual assessments of fluorine-18 fluorodeoxyglucose [ ¹⁸F]FDG-PET in individuals who meet appropriate use criteria for Alzheimer dementia (AD) biomarker assessments.

Methods

We performed a retrospective analysis of individuals with early-onset (age <65 years at onset) and/or atypical dementia (features other than memory at onset), who were evaluated at a tertiary care memory clinic. All participants underwent measurements of CSF biomarkers (Aβ42, p-tau181, and total tau levels), as well as [ ¹⁸F]FDG-PET scans, amyloid-PET scans, and plasma p-tau217 quantifications. To determine whether the [ ¹⁸F]FDG-PET images were compatible with AD, images were visually rated by 2 nuclear medicine experts. Using a contingency analysis, we evaluated the accuracy of [ ¹⁸F]FDG-PET scan interpretation and plasma p-tau217 for an AD biomarker profile in CSF and for amyloid-PET positivity.

Results

A total of 81 individuals with early onset and/or atypical dementia were included in this study (mean age = 65 years; 48/81 female (59%). Both [ ¹⁸F]FDG-PET and plasma p-tau217 showed high levels of agreement with reference standard AD biomarkers ([ ¹⁸F]FDG-PET area under the curve [AUC]: 71%; plasma p-tau217 AUC: 81%). Although both biomarkers had similar specificity for AD [ ¹⁸F]FDG-PET: 70%, CI: 0.56–0.81; plasma p-tau217: 70%, CI: 0.56–0.81), plasma p-tau217 had higher sensitivity for AD (plasma p-tau217: 97%, CI: 0.85–0.99 vs [ ¹⁸F]FDG-PET: 73%, CI: 0.57–0.85) ( p = 0.01). Overall accuracy was also higher for plasma p-tau217 (AUC = 84%, CI: 0.75–0.93 vs 72%, CI: 0.60–0.83 of [ ¹⁸F]FDG-PET) ( p = 0.02). The same pattern of results was observed when using amyloid-PET as the reference standard.

Discussion

Our study provides evidence that plasma p-tau217 has strong discriminative accuracy for AD among patients with early-onset and/or atypical dementia assessed in specialized settings. Future work should replicate these findings in secondary care settings.

Related collections

Most cited references 50

Record: found
Abstract: not found
Article: not found

Comparing the Areas under Two or More Correlated Receiver Operating Characteristic Curves: A Nonparametric Approach

David DeLong, Elizabeth Delong, Daniel L Clarke-Pearson (1988)

0 comments Cited 3472 times – based on 0 reviews      Review now

Bookmark

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.

0 comments Cited 3432 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.

0 comments Cited 3350 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Neurology

Journal ID (iso-abbrev): Neurology

Journal ID (hwp): neurology

Journal ID (publisher-id): NEUROLOGY

Title: Neurology

Publisher: Lippincott Williams & Wilkins (Hagerstown, MD )

ISSN (Print): 0028-3878

ISSN (Electronic): 1526-632X

Publication date (Print): 28 January 2025

Publication date (Electronic): 23 December 2024

Publication date PMC-release: 23 December 2024

Volume: 104

Issue: 2

Electronic Location Identifier: e210211

Affiliations

[1 ]Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada;

[2 ]Department of Experimental Medicine, McGill University;

[3 ]Montreal Neurological Institute;

[4 ]Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada;

[5 ]Graduate Program in Biological Sciences: Biochemistry (PPGBioq) and Pharmacology and Therapeutics (PPGFT), Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil;

[6 ]Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden;

[7 ]Wallenberg Centre for Molecular Medicine, University of Gothenburg, Gothenburg, Sweden;

[8 ]Department of Neurology and Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA;

[9 ]Lawrence Berkeley National Laboratory, Berkeley, CA;

[10 ]Department of Biofunctional Imaging, Hamamatsu University School of Medicine, Shizuoka, Japan;

[11 ]Department of Neurology, NHO Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan;

[12 ]Department of Specialized Medicine, McGill University, Montreal, Quebec, Canada;

[13 ]Department of Pharmacology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil;

[14 ]Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil;

[15 ]Centre hospitalier de l'Université de Montreal;

[16 ]Department of Psychiatry, McGill University, Montreal, Quebec, Canada;

[17 ]Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden;

[18 ]Department of Neurodegenerative Disease, UCL Institute of Neurology;

[19 ]UK Dementia Research Institute at UCL, London, United Kingdom;

[20 ]Hong Kong Center for Neurodegenerative Diseases, China; and

[21 ]Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI.

Author notes

Correspondence Dr. Rosa-Neto pedro.rosa@ 123456mcgill.ca

The Article Processing Charge was funded by CIHR.

Submitted and externally peer reviewed. The handling editor was Associate Editor Linda Hershey, MD, PhD, FAAN.

[*]

These authors contributed equally to this work.

Author information

Kely Monica Quispialaya https://orcid.org/0009-0000-6982-7143

Joseph Therriault https://orcid.org/0000-0002-7826-4781

Antonio Aliaga https://orcid.org/0009-0006-9792-7815

Andrea L. Benedet https://orcid.org/0000-0001-8219-1741

Nicholas J. Ashton https://orcid.org/0000-0002-3579-8804

Thomas Karikari https://orcid.org/0000-0003-1422-4358

Arthur Cassa Macedo https://orcid.org/0000-0002-3957-0284

Nesrine Rahmouni https://orcid.org/0009-0004-3081-8468

Cécile Tissot https://orcid.org/0000-0003-2711-3833

Lydia Trudel https://orcid.org/0009-0002-5593-7717

Seyyed Ali Hosseini https://orcid.org/0000-0001-7542-7541

Takashi Matsudaira https://orcid.org/0000-0002-6602-1301

Tevy Chan https://orcid.org/0009-0001-9134-5949

Tharick Pascoal https://orcid.org/0000-0001-9057-8014

Brian Gilfix https://orcid.org/0000-0001-5165-7422

Paolo Vitali https://orcid.org/0000-0001-8953-1542

Eduardo R. Zimmer https://orcid.org/0000-0002-5349-0053

Karine Provost https://orcid.org/0000-0002-5311-6758

Jean-Paul Soucy https://orcid.org/0000-0001-6979-1259

Serge Gauthier https://orcid.org/0000-0003-4272-3330

Henrik Zetterberg https://orcid.org/0000-0003-3930-4354

Kaj Blennow https://orcid.org/0000-0002-1890-4193

Pedro Rosa-Neto https://orcid.org/0000-0001-9116-1376

Article

Publisher ID: WNL-2024-101318

DOI: 10.1212/WNL.0000000000210211

PMC ID: 11666273

PubMed ID: 39715476

SO-VID: d6e05d0b-214f-4d23-b8b6-effe0ddb8bb1

License:

This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

History

Date received : 13 May 2024

Date accepted : 23 October 2024

Custom metadata

OPEN-ACCESS TRUE

Data availability:

Comments

Comment on this article

scite_

Smart Citations

Citing PublicationsSupportingMentioningContrasting

View Citations

See how this article has been cited at scite.ai

scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.

Most referenced authors 1,148

See all reference authors