Tau-neurodegeneration mismatch reveals vulnerability and resilience to comorbidities in Alzheimer's continuum.
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ABSTRACT: Introduction
Variability in relationship of tau-based neurofibrillary tangles (T) and neurodegeneration (N) in Alzheimer's disease (AD) arises from non-specific nature of N, modulated by non-AD co-pathologies, age-related changes, and resilience factors.Methods
We used regional T-N residual patterns to partition 184 patients within the Alzheimer's continuum into data-driven groups. These were compared with groups from 159 non-AD (amyloid "negative") patients partitioned using cortical thickness, and groups in 98 patients with ante mortem MRI and post mortem tissue for measuring N and T, respectively. We applied the initial T-N residual model to classify 71 patients in an independent cohort into predefined groups.Results
AD groups displayed spatial T-N mismatch patterns resembling neurodegeneration patterns in non-AD groups, similarly associated with non-AD factors and diverging cognitive outcomes. In the autopsy cohort, limbic T-N mismatch correlated with TDP-43 co-pathology.Discussion
T-N mismatch may provide a personalized approach for determining non-AD factors associated with resilience/vulnerability in AD.
SUBMITTER: Lyu X
PROVIDER: S-EPMC10984442 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
Publications
Tau-neurodegeneration mismatch reveals vulnerability and resilience to comorbidities in Alzheimer's continuum.
Lyu Xueying X Duong Michael Tran MT Xie Long L de Flores Robin R Richardson Hayley H Hwang Gyujoon G Wisse Laura E M LEM DiCalogero Michael M McMillan Corey T CT Robinson John L JL Xie Sharon X SX Lee Edward B EB Irwin David J DJ Dickerson Bradford C BC Davatzikos Christos C Nasrallah Ilya M IM Yushkevich Paul A PA Wolk David A DA Das Sandhitsu R SR
Alzheimer's & dementia : the journal of the Alzheimer's Association 20231205 3
<h4>Introduction</h4>Variability in relationship of tau-based neurofibrillary tangles (T) and neurodegeneration (N) in Alzheimer's disease (AD) arises from non-specific nature of N, modulated by non-AD co-pathologies, age-related changes, and resilience factors.<h4>Methods</h4>We used regional T-N residual patterns to partition 184 patients within the Alzheimer's continuum into data-driven groups. These were compared with groups from 159 non-AD (amyloid "negative") patients partitioned using cor ...[more]
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