Baseline β‐amyloid and tau predict longitudinal tau accumulation at different stages of Alzheimer’s disease

Abstract

AbstractBackgroundPrevious literatures suggest that β‐amyloid (Aβ) plaques, initial tau levels, age and Klotho‐VS heterozygosity (KL‐VShet) may be related to longitudinal tau accumulation in Alzheimer’s disease (AD), but it is still not fully understood how they predict tau replication in medial temporal cortex and propagations from the medial temporal lobe to inferior/middle temporal cortices at different stages of AD.MethodWe classified 325 Aβ PET positive (A+) ADNI participants into 143 A+/T‐and 182 A+/T+ according to the threshold (≥1.25) of Temporal‐metaROI 18F‐flortaucipir (FTP) standardized uptake value ratio (SUVR). Besides, 162 A‐/T‐ cognitive unimpaired participants without evidence of neurodegeneration were included as the reference group (Ref). We compared baseline and slopes of Aβ Centiloids and FTP SUVRs in 6 regions within Temporal‐metaROI with the Ref, and also investigated the prediction of longitudinal FTP SUVR changes by baseline Aβ Centiloids and FTP SUVRs in A+/T‐ and A+/T+ groups. Furthermore, we determined how age (Age<65 and Age≥65 years) and KL‐VShet haplotype (KL‐VShet+ and KL‐VShet‐) affect these associations.ResultA+/T‐ showed significantly or marginally higher tau and faster tau increases in amygdala, entorhinal and parahippocampus than the Ref (Figure 1). Both baseline Aβ and entorhinal tau predicted faster rates of FTP SUVR increases in amygdala, entorhinal and parahippocampus in A+/T‐. While entorhinal tau predicted faster FTP SUVR increases in all the cortical regions within Temporal‐metaROI in A+/T+, baseline Aβ predicted faster FTP SUVR increases in fusiform, inferior and middle temporal regions (Figure 2). Additionally, younger ages showed faster baseline Aβ‐related whereas older ages had more tau‐related longitudinal FTP SUVR increases in fusiform and inferior temporal regions (Figure 3). KL‐VShet+ individuals exhibited attenuated entorhinal tau‐related FTP SUVR increases in fusiform and inferior temporal regions than the KL‐VShet‐ individuals (Figure 4).ConclusionAβ plaques and initial tau tangles may play different roles in tau replication and propagation in A+/T‐ and A+/T+ individuals, and may interact differently with age at prediction longitudinal tau accumulation. KL‐VShet may attenuated tau accumulation via modulating entorhinal tau‐related tau propagation. These findings may provide novel insights into understanding how tau tangles replicate and propagate in Temporal‐metaROI region at different stages of AD.