Sequential 18 F-AV45/ 18 F-AV1451 dual-tracer brain PET imaging in Alzheimer's disease: amyloid-tau deposition, diagnostic performance, cognitive associations, and modulation by APOE ε4.
Combined amyloid-tau PET distinguished Alzheimer's disease from healthy controls with high accuracy
Sequential 18 F-AV45/ 18 F-AV1451 dual-tracer brain PET imaging in Alzheimer's disease: amyloid-tau deposition, diagnostic performance, cognitive associations, and modulation by APOE ε4.
Alzheimer's disease (AD) is neuropathologically defined by amyloid- β (Aβ) plaques and tau neurofibrillary tangles.
This study aimed to characterize Aβ-tau deposition, evaluate the pathological discriminatory performance of dual-tracer PET for typical amnestic AD, investigate cognitive correlations, and examine the modulatory role of APOE ε4 in a large clinical cohort.
We conducted a retrospective cross-sectional study of 438 participants, including 325 AD patients, 68 mild cognitive impairment (mild cognitive impairment) patients, and 45 healthy controls (healthy controls).
AUROC scale, 1.0 is perfect, PET nearly perfectly separates AD from controls
Whole-brain and regional SUVRs for both tracers were significantly higher in AD than in mild cognitive impairment and healthy controls (all p < 0.001), with peak uptake in the temporoparietal lobe.
Tau burden and APOE ε4 were independent predictors of cognitive impairment.
Aβ and tau SUVRs were strongly correlated ( r = 0.65-0.81), most prominently in the precuneus and inferior temporal gyrus.
APOE ε4 carriers exhibited significantly higher Aβ and tau deposition.
Sequential 18 F-AV45/ 18 F-AV1451 dual-tracer PET enables accurate in vivo characterization of AD-related Aβ-tau pathology, and standardized combined analysis further improves its ability to distinguish typical sporadic amnestic AD from other groups.
Tau is an independent driver of cognitive decline, while Aβ remains relevant for amyloid-targeted therapies. APOE ε4 modulates Aβ-tau interactions.
Dual-tracer PET is a robust tool for clinical AD evaluation, pathological staging, and therapeutic monitoring of typical amnestic AD.