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Tau-neurodegeneration mismatch reveals vulnerability and resilience to comorbidities in Alzheimer's continuum

Lyu, Xueying ; Duong, Michael Tran ; Xie, Long ; de Flores, Robin ; Richardson, Hayley ; Hwang, Gyujoon ; Wisse, Laura E.M. LU orcid ; DiCalogero, Michael ; McMillan, Corey T. and Robinson, John L. , et al. (2023) In Alzheimer's and Dementia
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
aging, Alzheimer's disease, co-pathologies, multi-modality imaging, neurodegeneration, post mortem, tau
in
Alzheimer's and Dementia
publisher
Wiley
external identifiers
  • pmid:38050662
  • scopus:85161816922
ISSN
1552-5260
DOI
10.1002/alz.13559
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
id
70e2c81d-ea46-476a-81b9-93b4e0838cfe
date added to LUP
2024-01-15 12:50:36
date last changed
2024-04-16 03:00:02
@article{70e2c81d-ea46-476a-81b9-93b4e0838cfe,
  abstract     = {{<p>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.</p>}},
  author       = {{Lyu, Xueying and Duong, Michael Tran and Xie, Long and de Flores, Robin and Richardson, Hayley and Hwang, Gyujoon and Wisse, Laura E.M. and DiCalogero, Michael and McMillan, Corey T. and Robinson, John L. and Xie, Sharon X. and Lee, Edward B. and Irwin, David J. and Dickerson, Bradford C. and Davatzikos, Christos and Nasrallah, Ilya M. and Yushkevich, Paul A. and Wolk, David A. and Das, Sandhitsu R.}},
  issn         = {{1552-5260}},
  keywords     = {{aging; Alzheimer's disease; co-pathologies; multi-modality imaging; neurodegeneration; post mortem; tau}},
  language     = {{eng}},
  publisher    = {{Wiley}},
  series       = {{Alzheimer's and Dementia}},
  title        = {{Tau-neurodegeneration mismatch reveals vulnerability and resilience to comorbidities in Alzheimer's continuum}},
  url          = {{http://dx.doi.org/10.1002/alz.13559}},
  doi          = {{10.1002/alz.13559}},
  year         = {{2023}},
}