ABSTRACT

Objective: To use a cluster analysis of [18F]AV-1451 tau-PET data to determine how subjects with Alzheimer’s disease vary in the relative involvement of the entorhinal cortex and neocortex, and determine whether relative involvement of these two regions can help explain variability in age and clinical phenotype in Alzheimer’s disease.

METHODS: We calculated [18F]AV-1451 uptake in entorhinal cortex and neocortex in 62 amyloid-positive Alzheimer’s disease patients (39 typical and 23 atypical presentation). Tau-PET values were normalized to the cerebellum to create SUVRs. Tau-PET SUVRs were log-transformed and clustered blinded to clinical information into three groups using K-median cluster analysis. Demographics, clinical phenotype, cognitive performance, and apolipoprotein e4 frequency were compared across clusters.

RESULTS: The cluster analysis identified a cluster with low entorhinal and cortical uptake (ELo/CLo), one with low entorhinal but high cortical uptake (ELo/CHi), and one with high cortical and entorhinal uptake (EHi/CHi). Clinical phenotype differed across clusters, with typical AD most commonly observed in the ELo/CLo and EHi/CHi clusters, and atypical AD most commonly observed in the ELo/CHi cluster. The ELo/CLo cluster had an older age at PET and onset than the other clusters. The apolipoprotein e4 frequency was lower in the ELo/CHi cluster. The EHi/CHi cluster had the worst memory impairment, while the ELo/CHi cluster had the worst impairment in non-memory domains.

INTERPRETATION: This study demonstrates considerable variability in [18F]AV-1451 tau-PET uptake in AD, but shows that a straight-forward clustering based on entorhinal and cortical uptake maps well onto age and clinical presentation in AD. This article is protected by copyright. All rights reserved.

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