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Targeting pre-symptomatic AD individuals: Deep cognitiveassessment and plasma biomarkers to predict tau aggregation

Title: Targeting pre-symptomatic AD individuals: Deep cognitiveassessment and plasma biomarkers to predict tau aggregation
Authors: Quenon, Lisa; Huyghe, Lara; Bayart, Jean-Louis; Boyer, Emilien; Colmant, Lise; Salman, Yasmine; Gérard, Thomas; Malotaux, Vincent; Delhaye, Emma; Besson, Gabriel; Dricot, Laurence; Lhommel, Renaud; Ivanoiu, Adrian; Bastin, Christine; Hanseeuw, Bernard J.
Source: Alzheimer's and Dementia: the Journal of the Alzheimer's Association, 21 (S2), e098968 (2025-12); Alzheimer's Association International Conference, 2025
Publisher Information: Wiley
Publication Year: 2025
Collection: University of Liège: ORBi (Open Repository and Bibliography)
Subject Terms: Aged; Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Brain; Cognitive Dysfunction; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Positron-Emission Tomography; tau Proteins; 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: peer reviewed ; BACKGROUND: Cognitively unimpaired (CU) individuals with both elevated brain amyloid load and tau burden in the medial temporal (MTL) and temporal neocortex (NEO) face high risk of short-term cognitive decline (≤5 years; risk=50%). However, identifying these individuals in the population remains challenging due to their low prevalence (8-10%), the cost and invasiveness of validated biomarkers. Cognitive measures and blood-based biomarkers offer promising scalable alternatives, but most plasma biomarkers are more closely associated with amyloid than tau aggregates, and tau-specific measures remain poorly defined. This study assessed whether specific cognitive tasks, including tasks targeting the functions of the first affected regions by tauopathy, and blood-based biomarkers can predict early tau aggregation. METHOD: Seventy-seven CU participants completed the Visual Short-Term Binding Test (VSTMBT), the Conceptual Matching Task (CMT), the cognitive tests required for the Preclinical Alzheimer's Cognitive Composite (PACC5), a blood-test, [18F]-MK6240 tau-PET imaging, 3T-MRI, and amyloid (A) status determination (A+ for Centiloid≥ 20 or cerebrospinal fluid amyloid-beta42≤437 pg/mL). The VSTMBT and CMT (Figure 1) involve fined-grained perceptual and conceptual discrimination, respectively, supposedly relying on the transentorhinal cortex. The sample included 55 A- CU and 22 A+ CU (Table 1). Standard Uptake Value ratios (SUVr) were computed for MTL and temporal NEO region of interests (ROI; Ossenkoppele et al., 2022; reference=grey cerebellar). Plasma p-tau217 and p-tau181 levels were quantified using Lumipulse and SIMOA. Univariate regression models predicting ROI tau burden based on demographics (age, sex, education), cognitive performance (VSTMBT, CMT, PACC5), and plasma p-tau species (2 ROIs x 8 predictors) were conducted to select contributing predictors (highlighted in green in Table 2) for further stepwise regression analyses (both directions). RESULT: For MTL tau burden, optimal model fit ...
Document Type: conference object; report
Language: English
ISSN: 1552-5260; 1552-5279
Relation: urn:issn:1552-5260; urn:issn:1552-5279; https://orbi.uliege.be/handle/2268/339249; info:hdl:2268/339249; info:pmid:41445369
DOI: 10.1002/alz70856_098968
Availability: https://orbi.uliege.be/handle/2268/339249; https://orbi.uliege.be/bitstream/2268/339249/1/Alzheimer%20s%20%20%20Dementia%20-%202025%20-%20Quenon%20-%20Targeting%20pre%e2%80%90symptomatic%20AD%20individuals%20%20Deep%20cognitive%20assessment%20and%20plasma.pdf; https://doi.org/10.1002/alz70856_098968
Rights: open access ; http://purl.org/coar/access_right/c_abf2 ; info:eu-repo/semantics/openAccess
Accession Number: edsbas.28538BD
Database: BASE