| Title: |
Targeting pre-symptomatic AD individuals: Deep cognitive assessment 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 & Dementia Publications; 2025 Supplement, Vol. 21, p1-4, 4p, 1 Color Photograph, 2 Charts |
| Subject Terms: |
ALZHEIMER'S disease; BIOMARKERS; BLOOD serum analysis; TAUOPATHIES; AT-risk people; TAU proteins; COGNITION disorders; COGNITIVE testing |
| Abstract: |
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 ROIsx 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 (initial AIC=4.88, final AIC=3.55) was found with the VSTMBT (b = -0.01, SE=0.004, p = .004) and plasma p-tau217 level (b = 1.18, SE=0.276, p |
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| Database: |
Complementary Index |