Brain atrophy in primary age-related tauopathy is linked to transactive response DNA-binding protein of 43 kDa

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Abstract

Introduction: Primary age-related tauopathy (PART) is characterized by the presence of neurofibrillary tangles and absent-minimal β-amyloid deposition. Transactive response DNA-binding protein of 43 kDa (TDP-43), a third protein, has recently garnished a lot of attention in Alzheimer's disease where it is associated with memory loss and amygdala and hippocampal atrophy. We aimed to determine whether TDP-43 is associated with brain atrophy in PART. Methods: We assessed the frequency of TDP-43 in PART and performed voxel-level analysis in SPM12, as well as region-of-interest analysis using linear regression modeling, controlling for variables of interest, to assess for associations between TDP-43 and brain atrophy. Results: Of 116 PART cases, 31 (26.7%) had TDP-43. The presence of TDP-43 was associated with significantly greater amygdala, hippocampal, and anterior temporal atrophy in both the region-of-interest and the voxel level analyses. Discussion: TDP-43 is associated with greater brain atrophy in PART.

Original languageEnglish (US)
JournalAlzheimer's and Dementia
DOIs
StatePublished - Jan 1 2019

Fingerprint

Tauopathies
DNA-Binding Proteins
Atrophy
Brain
Amygdala
Neurofibrillary Tangles
Memory Disorders
Amyloid
Linear Models
Alzheimer Disease
Proteins

Keywords

  • Atrophy
  • Hippocampus
  • MRI
  • PART
  • Tauopathy
  • TDP-43

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

Cite this

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title = "Brain atrophy in primary age-related tauopathy is linked to transactive response DNA-binding protein of 43 kDa",
abstract = "Introduction: Primary age-related tauopathy (PART) is characterized by the presence of neurofibrillary tangles and absent-minimal β-amyloid deposition. Transactive response DNA-binding protein of 43 kDa (TDP-43), a third protein, has recently garnished a lot of attention in Alzheimer's disease where it is associated with memory loss and amygdala and hippocampal atrophy. We aimed to determine whether TDP-43 is associated with brain atrophy in PART. Methods: We assessed the frequency of TDP-43 in PART and performed voxel-level analysis in SPM12, as well as region-of-interest analysis using linear regression modeling, controlling for variables of interest, to assess for associations between TDP-43 and brain atrophy. Results: Of 116 PART cases, 31 (26.7{\%}) had TDP-43. The presence of TDP-43 was associated with significantly greater amygdala, hippocampal, and anterior temporal atrophy in both the region-of-interest and the voxel level analyses. Discussion: TDP-43 is associated with greater brain atrophy in PART.",
keywords = "Atrophy, Hippocampus, MRI, PART, Tauopathy, TDP-43",
author = "Josephs, {Keith Anthony} and Murray, {Melissa E} and Nirubol Tosakulwong and Weigand, {Stephen D.} and Knopman, {David S} and Petersen, {Ronald Carl} and Jack, {Clifford R Jr.} and Whitwell, {Jennifer Lynn} and Dickson, {Dennis W}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.jalz.2019.03.003",
language = "English (US)",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
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TY - JOUR

T1 - Brain atrophy in primary age-related tauopathy is linked to transactive response DNA-binding protein of 43 kDa

AU - Josephs, Keith Anthony

AU - Murray, Melissa E

AU - Tosakulwong, Nirubol

AU - Weigand, Stephen D.

AU - Knopman, David S

AU - Petersen, Ronald Carl

AU - Jack, Clifford R Jr.

AU - Whitwell, Jennifer Lynn

AU - Dickson, Dennis W

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Introduction: Primary age-related tauopathy (PART) is characterized by the presence of neurofibrillary tangles and absent-minimal β-amyloid deposition. Transactive response DNA-binding protein of 43 kDa (TDP-43), a third protein, has recently garnished a lot of attention in Alzheimer's disease where it is associated with memory loss and amygdala and hippocampal atrophy. We aimed to determine whether TDP-43 is associated with brain atrophy in PART. Methods: We assessed the frequency of TDP-43 in PART and performed voxel-level analysis in SPM12, as well as region-of-interest analysis using linear regression modeling, controlling for variables of interest, to assess for associations between TDP-43 and brain atrophy. Results: Of 116 PART cases, 31 (26.7%) had TDP-43. The presence of TDP-43 was associated with significantly greater amygdala, hippocampal, and anterior temporal atrophy in both the region-of-interest and the voxel level analyses. Discussion: TDP-43 is associated with greater brain atrophy in PART.

AB - Introduction: Primary age-related tauopathy (PART) is characterized by the presence of neurofibrillary tangles and absent-minimal β-amyloid deposition. Transactive response DNA-binding protein of 43 kDa (TDP-43), a third protein, has recently garnished a lot of attention in Alzheimer's disease where it is associated with memory loss and amygdala and hippocampal atrophy. We aimed to determine whether TDP-43 is associated with brain atrophy in PART. Methods: We assessed the frequency of TDP-43 in PART and performed voxel-level analysis in SPM12, as well as region-of-interest analysis using linear regression modeling, controlling for variables of interest, to assess for associations between TDP-43 and brain atrophy. Results: Of 116 PART cases, 31 (26.7%) had TDP-43. The presence of TDP-43 was associated with significantly greater amygdala, hippocampal, and anterior temporal atrophy in both the region-of-interest and the voxel level analyses. Discussion: TDP-43 is associated with greater brain atrophy in PART.

KW - Atrophy

KW - Hippocampus

KW - MRI

KW - PART

KW - Tauopathy

KW - TDP-43

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