Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
Uncovering distinct spatiotemporal trajectories of T-N mismatch subtypes with likely co-pathology in Alzheimer's disease using event-based modeling.
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Lyu Xueying, Brown Christopher A, Duong Michael Tran, Fischer Emma P, McGrew Emily, Irwin David J, Dickerson Bradford C, Nasrallah Ilya M, Shinohara Russell Takeshi, Young Alexandra L, Yushkevich Paul A, Das Sandhitsu R, Wolk David A, Alzheimer's Disease Neuroimaging Initiative
Аннотация
INTRODUCTION: In Alzheimer's disease (AD), tau-neurodegeneration (T-N) mismatch has been proposed to reflect non-AD processes such as transactive response DNA binding protein 43 kDa and vascular disease. We aimed to characterize the spatiotemporal trajectories of T-N mismatch that may reflect non-AD progression.
METHODS: We performed T-N regression on 710 Alzheimer's Disease Neuroimaging Initiative participants using cortical thickness and 18F-flortaucipir uptake across 20 cortical regions. SuStaIn, a data-driven phenotype discovery and staging algorithm, was applied to standardized T-N residuals in canonical (N∼T) and vulnerable (N > T) cases.
RESULTS: SuStaIn identified three vulnerable subtypes with distinct N > T progression patterns. The posterior and anterior subtypes displayed different, but progressively diffuse mismatch patterns, while the limbic subtype exhibited temporal-limbic progression. Subtypes and SuStaIn stages were associated with distinct clinical features. Their longitudinal trajectories aligned with SuStaIn inferred progression.
DISCUSSION: Findings support that T-N mismatch progression captures specific co-pathological processes.
METHODS: We performed T-N regression on 710 Alzheimer's Disease Neuroimaging Initiative participants using cortical thickness and 18F-flortaucipir uptake across 20 cortical regions. SuStaIn, a data-driven phenotype discovery and staging algorithm, was applied to standardized T-N residuals in canonical (N∼T) and vulnerable (N > T) cases.
RESULTS: SuStaIn identified three vulnerable subtypes with distinct N > T progression patterns. The posterior and anterior subtypes displayed different, but progressively diffuse mismatch patterns, while the limbic subtype exhibited temporal-limbic progression. Subtypes and SuStaIn stages were associated with distinct clinical features. Their longitudinal trajectories aligned with SuStaIn inferred progression.
DISCUSSION: Findings support that T-N mismatch progression captures specific co-pathological processes.