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Discrimination tasks increase the value of plasma p‐tau217 to predict presymptomatic Alzheimer's disease

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Title: Discrimination tasks increase the value of plasma p‐tau217 to predict presymptomatic Alzheimer's disease
Authors: Huyghe, Lara, Quenon, Lisa, Bayart, Jean-Louis, Colmant, Lise, Boyer, Emilien, Gérard, Thomas, Salman, Yasmine, Besson, Gabriel, Dricot, Laurence, Lhommel, Renaud, Ivanoiu, Adrian, Bastin, Christine, Delhaye, Emma, Hanseeuw, Bernard J
Source: Alzheimer's and Dementia: the Journal of the Alzheimer's Association, 21 Suppl 8 (Suppl 8), e109967 (2025-12); Alzheimer's Association International Conference, 2025
Publisher Information: Wiley, 2025.
Publication Year: 2025
Subject Terms: tau Proteins, Biomarkers, Amyloid beta-Peptides, Humans, Positron-Emission Tomography, Male, Female, Aged, Biomarkers/blood, Amyloid beta-Peptides/blood, Neuropsychological Tests, Aged, 80 and over, Middle Aged, Alzheimer Disease/diagnostic imaging, Alzheimer Disease/blood, Alzheimer Disease/diagnosis, tau Proteins/blood, Brain/diagnostic imaging, Brain/metabolism, Alzheimer Disease, Brain, Epidemiology, Health Policy, Developmental Neuroscience, Neurology (clinical), Geriatrics and Gerontology, Cellular and Molecular Neuroscience, Psychiatry and Mental Health, Social & behavioral sciences, psychology, Neurosciences & behavior, Sciences sociales & comportementales, psychologie, Neurosciences & comportement
Description: [en] BACKGROUND: AD can be diagnosed using amyloid (Aβ) and tau-PET imaging. These techniques are expensive and invasive, making them hardly practical for screening in clinically unimpaired (CU) populations. Research is therefore focused on developing more affordable methods to detect pre-symptomatic AD pathology. Specific cognitive metrics and diverse blood-based biomarkers, including soluble phosphorylated tau (p-tau) species, have emerged as promisingly reflecting an underlying aggregated Aβ or tau pathology in the brain. However, head-to-head comparisons between these measures are relatively scarce and their additive value to detect incipient AD pathology is largely undetermined. We aimed to investigate the value of plasma p-tau217 and cognitive tasks assessing perceptual or conceptual discrimination to identify CU individuals with PET-imaging evidence of AD pathology.METHOD: Eighty CU older adults underwent a blood test for plasma p-tau217, Aβ40 and Aβ42, [18F]-MK6240 tau-PET, [18F]-Flutemetamol or [11C]-PIB amyloid-PET, 3D-T1 brain MRI, a neuropsychological assessment including PACC5, the Conceptual Matching Task (CMT), and the Visual-Short Term Memory Binding Test (VSTMBT). These tasks evaluate conceptual and perceptual discrimination abilities respectively (Figure 1). Participants were classified based on Aβ status [Centiloid<20: Aβ- (n = 55) and Centiloid>20: Aβ+ (n = 25)] or tau-PET visual Braak stage [Braak=0: Tau-CU (n = 65) and Braak>0: Tau+CU (n = 15)]. ROC curves were computed to determine optimal threshold, sensitivity, and specificity of each test. We also performed logistic regression models with receiver operating characteristic (ROC) curves to determine the accuracy of plasma biomarkers and cognitive measures in differentiating Aβ-PET and tau-PET status.RESULT: p-tau217 was the measure with the larger AUC for detecting incipient amyloidosis or tauopathy as evidenced using PET (AUC=0.91). Among cognitive measures, VSTMBT was the most sensitive and accurate measure for detecting Aβ (AUC=.722) and tau-PET positivity (AUC=0.743) (Figure 2). The combined use of plasma and cognitive markers (Figure 3) allows predicting AD pathology in clinically unimpaired individuals (AUC=0.93 for Aβ and AUC =0.95 for tau). Specifically, the addition of very subtle cognitive deficits to pTau217 allowed increasing sensitivity for positive tau-PET from 0.83 to 1.0 (with specificity=0.91).CONCLUSION: The combined use of plasma markers and cognitive measures looks promising for the early diagnosis of Alzheimer's disease.
Document Type: conference paper
http://purl.org/coar/resource_type/c_5794
conferenceObject
peer reviewed
Language: English
Relation: https://alz-journals.onlinelibrary.wiley.com/doi/pdf/10.1002/alz70862_109967; urn:issn:1552-5260; urn:issn:1552-5279
DOI: 10.1002/alz70862_109967
Access URL: https://orbi.uliege.be/handle/2268/339247
Rights: open access
http://purl.org/coar/access_right/c_abf2
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Accession Number: edsorb.339247
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  Data: Alzheimer&#39;s and Dementia: the Journal of the Alzheimer&#39;s Association, 21 Suppl 8 (Suppl 8), e109967 (2025-12); Alzheimer&#39;s Association International Conference, 2025
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– Name: Abstract
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  Group: Ab
  Data: [en] BACKGROUND: AD can be diagnosed using amyloid (Aβ) and tau-PET imaging. These techniques are expensive and invasive, making them hardly practical for screening in clinically unimpaired (CU) populations. Research is therefore focused on developing more affordable methods to detect pre-symptomatic AD pathology. Specific cognitive metrics and diverse blood-based biomarkers, including soluble phosphorylated tau (p-tau) species, have emerged as promisingly reflecting an underlying aggregated Aβ or tau pathology in the brain. However, head-to-head comparisons between these measures are relatively scarce and their additive value to detect incipient AD pathology is largely undetermined. We aimed to investigate the value of plasma p-tau217 and cognitive tasks assessing perceptual or conceptual discrimination to identify CU individuals with PET-imaging evidence of AD pathology.METHOD: Eighty CU older adults underwent a blood test for plasma p-tau217, Aβ40 and Aβ42, [18F]-MK6240 tau-PET, [18F]-Flutemetamol or [11C]-PIB amyloid-PET, 3D-T1 brain MRI, a neuropsychological assessment including PACC5, the Conceptual Matching Task (CMT), and the Visual-Short Term Memory Binding Test (VSTMBT). These tasks evaluate conceptual and perceptual discrimination abilities respectively (Figure 1). Participants were classified based on Aβ status [Centiloid&lt;20: Aβ- (n&#160;=&#160;55) and Centiloid&gt;20: Aβ+ (n&#160;=&#160;25)] or tau-PET visual Braak stage [Braak=0: Tau-CU (n&#160;=&#160;65) and Braak&gt;0: Tau+CU (n&#160;=&#160;15)]. ROC curves were computed to determine optimal threshold, sensitivity, and specificity of each test. We also performed logistic regression models with receiver operating characteristic (ROC) curves to determine the accuracy of plasma biomarkers and cognitive measures in differentiating Aβ-PET and tau-PET status.RESULT: p-tau217 was the measure with the larger AUC for detecting incipient amyloidosis or tauopathy as evidenced using PET (AUC=0.91). Among cognitive measures, VSTMBT was the most sensitive and accurate measure for detecting Aβ (AUC=.722) and tau-PET positivity (AUC=0.743) (Figure 2). The combined use of plasma and cognitive markers (Figure 3) allows predicting AD pathology in clinically unimpaired individuals (AUC=0.93 for Aβ and AUC =0.95 for tau). Specifically, the addition of very subtle cognitive deficits to pTau217 allowed increasing sensitivity for positive tau-PET from 0.83 to 1.0 (with specificity=0.91).CONCLUSION: The combined use of plasma markers and cognitive measures looks promising for the early diagnosis of Alzheimer&#39;s disease.
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      – Type: doi
        Value: 10.1002/alz70862_109967
    Languages:
      – Text: English
    Subjects:
      – SubjectFull: tau Proteins
        Type: general
      – SubjectFull: Biomarkers
        Type: general
      – SubjectFull: Amyloid beta-Peptides
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      – SubjectFull: Amyloid beta-Peptides/blood
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      – SubjectFull: Neuropsychological Tests
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      – SubjectFull: Aged, 80 and over
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      – SubjectFull: Middle Aged
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      – SubjectFull: Alzheimer Disease/diagnostic imaging
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      – SubjectFull: Alzheimer Disease/blood
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      – SubjectFull: Alzheimer Disease/diagnosis
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      – SubjectFull: Brain/metabolism
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      – SubjectFull: Alzheimer Disease
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      – SubjectFull: Cellular and Molecular Neuroscience
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      – SubjectFull: Psychiatry and Mental Health
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      – SubjectFull: Social & behavioral sciences, psychology
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      – SubjectFull: Neurosciences & behavior
        Type: general
      – SubjectFull: Sciences sociales & comportementales, psychologie
        Type: general
      – SubjectFull: Neurosciences & comportement
        Type: general
    Titles:
      – TitleFull: Discrimination tasks increase the value of plasma p‐tau217 to predict presymptomatic Alzheimer's disease
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