MRI correlates of protein deposition and disease severity in postmortem frontotemporal lobar degeneration

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Abstract

Background: Frontotemporal lobar degeneration (FTLD) can be classified based on the presence of the microtubule-associated protein tau and the TAR DNA binding protein-43 (TDP-43). Future treatments will likely target these proteins, therefore it is important to identify biomarkers to help predict protein biochemistry. Objective: To determine whether there is an MRI signature pattern of tau or TDP-43 using a large cohort of FTLD subjects and to investigate how patterns of atrophy change according to disease severity using a large autopsy-confirmed cohort of FTLD subjects. Methods: Patterns of gray matter loss were assessed using voxel-based morphometry in 37 tau-positive and 44 TDP-43-positive subjects compared to 35 age and gender-matched controls, and compared to each other. Comparisons were also repeated in behavioral variant frontotemporal dementia (bvFTD) subjects (n = 15 tau-positive and n = 30 TDP-43-positive). Patterns of atrophy were also assessed according to performance on the Clinical Dementia Rating (CDR) scale and Mini-Mental State Examination (MMSE). Results: The tau-positive and TDP-43-positive groups showed patterns of frontotemporal gray matter loss compared to controls with no differences observed between the groups, for all subjects and for bvFTD subjects. Patterns of gray matter loss increased in a graded manner by CDR and MMSE with loss in the frontal lobes, insula and hippocampus in mild subjects, spreading to the temporal and parietal cortices and striatum in more advanced disease. Conclusion: There is no signature pattern of atrophy for tau or TDP-43; however, patterns of atrophy in FTLD progress with measures of clinical disease severity.

Original languageEnglish (US)
Pages (from-to)106-117
Number of pages12
JournalNeurodegenerative Diseases
Volume6
Issue number3
DOIs
StatePublished - May 2009

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Frontotemporal Lobar Degeneration
DNA-Binding Proteins
Atrophy
Frontotemporal Dementia
Proteins
Dementia
Parietal Lobe
Microtubule-Associated Proteins
Frontal Lobe
Temporal Lobe
Biochemistry
Autopsy
Hippocampus
Biomarkers
Gray Matter

Keywords

  • Autopsy
  • Clinical Dementia Rating Scale
  • Frontotemporal lobar degeneration
  • Mini-Mental State Examination
  • TAR DNA binding protein-43
  • Tau
  • Voxel-based morphometry

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

@article{14effa6150bb45aabfe4e55e4b345d88,
title = "MRI correlates of protein deposition and disease severity in postmortem frontotemporal lobar degeneration",
abstract = "Background: Frontotemporal lobar degeneration (FTLD) can be classified based on the presence of the microtubule-associated protein tau and the TAR DNA binding protein-43 (TDP-43). Future treatments will likely target these proteins, therefore it is important to identify biomarkers to help predict protein biochemistry. Objective: To determine whether there is an MRI signature pattern of tau or TDP-43 using a large cohort of FTLD subjects and to investigate how patterns of atrophy change according to disease severity using a large autopsy-confirmed cohort of FTLD subjects. Methods: Patterns of gray matter loss were assessed using voxel-based morphometry in 37 tau-positive and 44 TDP-43-positive subjects compared to 35 age and gender-matched controls, and compared to each other. Comparisons were also repeated in behavioral variant frontotemporal dementia (bvFTD) subjects (n = 15 tau-positive and n = 30 TDP-43-positive). Patterns of atrophy were also assessed according to performance on the Clinical Dementia Rating (CDR) scale and Mini-Mental State Examination (MMSE). Results: The tau-positive and TDP-43-positive groups showed patterns of frontotemporal gray matter loss compared to controls with no differences observed between the groups, for all subjects and for bvFTD subjects. Patterns of gray matter loss increased in a graded manner by CDR and MMSE with loss in the frontal lobes, insula and hippocampus in mild subjects, spreading to the temporal and parietal cortices and striatum in more advanced disease. Conclusion: There is no signature pattern of atrophy for tau or TDP-43; however, patterns of atrophy in FTLD progress with measures of clinical disease severity.",
keywords = "Autopsy, Clinical Dementia Rating Scale, Frontotemporal lobar degeneration, Mini-Mental State Examination, TAR DNA binding protein-43, Tau, Voxel-based morphometry",
author = "Whitwell, {Jennifer Lynn} and Jack, {Clifford R Jr.} and Senjem, {Matthew L.} and Parisi, {Joseph E} and Boeve, {Bradley F} and Knopman, {David S} and Dickson, {Dennis W} and Petersen, {Ronald Carl} and Josephs, {Keith Anthony}",
year = "2009",
month = "5",
doi = "10.1159/000209507",
language = "English (US)",
volume = "6",
pages = "106--117",
journal = "Neurodegenerative Diseases",
issn = "1660-2854",
publisher = "S. Karger AG",
number = "3",

}

TY - JOUR

T1 - MRI correlates of protein deposition and disease severity in postmortem frontotemporal lobar degeneration

AU - Whitwell, Jennifer Lynn

AU - Jack, Clifford R Jr.

AU - Senjem, Matthew L.

AU - Parisi, Joseph E

AU - Boeve, Bradley F

AU - Knopman, David S

AU - Dickson, Dennis W

AU - Petersen, Ronald Carl

AU - Josephs, Keith Anthony

PY - 2009/5

Y1 - 2009/5

N2 - Background: Frontotemporal lobar degeneration (FTLD) can be classified based on the presence of the microtubule-associated protein tau and the TAR DNA binding protein-43 (TDP-43). Future treatments will likely target these proteins, therefore it is important to identify biomarkers to help predict protein biochemistry. Objective: To determine whether there is an MRI signature pattern of tau or TDP-43 using a large cohort of FTLD subjects and to investigate how patterns of atrophy change according to disease severity using a large autopsy-confirmed cohort of FTLD subjects. Methods: Patterns of gray matter loss were assessed using voxel-based morphometry in 37 tau-positive and 44 TDP-43-positive subjects compared to 35 age and gender-matched controls, and compared to each other. Comparisons were also repeated in behavioral variant frontotemporal dementia (bvFTD) subjects (n = 15 tau-positive and n = 30 TDP-43-positive). Patterns of atrophy were also assessed according to performance on the Clinical Dementia Rating (CDR) scale and Mini-Mental State Examination (MMSE). Results: The tau-positive and TDP-43-positive groups showed patterns of frontotemporal gray matter loss compared to controls with no differences observed between the groups, for all subjects and for bvFTD subjects. Patterns of gray matter loss increased in a graded manner by CDR and MMSE with loss in the frontal lobes, insula and hippocampus in mild subjects, spreading to the temporal and parietal cortices and striatum in more advanced disease. Conclusion: There is no signature pattern of atrophy for tau or TDP-43; however, patterns of atrophy in FTLD progress with measures of clinical disease severity.

AB - Background: Frontotemporal lobar degeneration (FTLD) can be classified based on the presence of the microtubule-associated protein tau and the TAR DNA binding protein-43 (TDP-43). Future treatments will likely target these proteins, therefore it is important to identify biomarkers to help predict protein biochemistry. Objective: To determine whether there is an MRI signature pattern of tau or TDP-43 using a large cohort of FTLD subjects and to investigate how patterns of atrophy change according to disease severity using a large autopsy-confirmed cohort of FTLD subjects. Methods: Patterns of gray matter loss were assessed using voxel-based morphometry in 37 tau-positive and 44 TDP-43-positive subjects compared to 35 age and gender-matched controls, and compared to each other. Comparisons were also repeated in behavioral variant frontotemporal dementia (bvFTD) subjects (n = 15 tau-positive and n = 30 TDP-43-positive). Patterns of atrophy were also assessed according to performance on the Clinical Dementia Rating (CDR) scale and Mini-Mental State Examination (MMSE). Results: The tau-positive and TDP-43-positive groups showed patterns of frontotemporal gray matter loss compared to controls with no differences observed between the groups, for all subjects and for bvFTD subjects. Patterns of gray matter loss increased in a graded manner by CDR and MMSE with loss in the frontal lobes, insula and hippocampus in mild subjects, spreading to the temporal and parietal cortices and striatum in more advanced disease. Conclusion: There is no signature pattern of atrophy for tau or TDP-43; however, patterns of atrophy in FTLD progress with measures of clinical disease severity.

KW - Autopsy

KW - Clinical Dementia Rating Scale

KW - Frontotemporal lobar degeneration

KW - Mini-Mental State Examination

KW - TAR DNA binding protein-43

KW - Tau

KW - Voxel-based morphometry

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U2 - 10.1159/000209507

DO - 10.1159/000209507

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VL - 6

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EP - 117

JO - Neurodegenerative Diseases

JF - Neurodegenerative Diseases

SN - 1660-2854

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