Does TDP-43 type confer a distinct pattern of atrophy in frontotemporal lobar degeneration?

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Abstract

Objective: To determine whether TDP-43 type is associated with distinct patterns of brain atrophy on MRI in subjects with pathologically confirmed frontotemporal lobar degeneration (FTLD). Methods: In this case-control study, we identified all subjects with a pathologic diagnosis of FTLD with TDP-43 immunoreactive inclusions (FTLD-TDP) and at least one volumetric head MRI scan (n = 42). In each case we applied published criteria for subclassification of FTLD-TDP into FTLD-TDP types 1-3. Voxel-based morphometry was used to compare subjects with each of the different FTLD-TDP types to age- and gender-matched normal controls (n = 30). We also assessed different pathologic and genetic variants within, and across, the different types. Results: Twenty-two subjects were classified as FTLD-TDP type 1, 9 as type 2, and 11 as type 3. We identified different patterns of atrophy across the types with type 1 showing frontotemporal and parietal atrophy, type 2 predominantly anterior temporal lobe atrophy, and type 3 predominantly posterior frontal atrophy. Within the FTLD-TDP type 1 group, those with a progranulin mutation had significantly more lateral temporal lobe atrophy than those without. All type 2 subjects were diagnosed with semantic dementia. Subjects with a pathologic diagnosis of FTLD with motor neuron degeneration had a similar pattern of atrophy, regardless of whether they were type 1 or type 3. Conclusions: Although there are different patterns of atrophy across the different FTLD-TDP types, it appears that genetic and pathologic factors may also affect the patterns of atrophy.

Original languageEnglish (US)
Pages (from-to)2212-2220
Number of pages9
JournalNeurology
Volume75
Issue number24
DOIs
StatePublished - Dec 14 2010

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Frontotemporal Lobar Degeneration
Atrophy
Temporal Lobe
Frontotemporal Dementia
Nerve Degeneration
Motor Neurons
Case-Control Studies
Head
Magnetic Resonance Imaging

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

@article{23b9b410950a4da388a555142adaf672,
title = "Does TDP-43 type confer a distinct pattern of atrophy in frontotemporal lobar degeneration?",
abstract = "Objective: To determine whether TDP-43 type is associated with distinct patterns of brain atrophy on MRI in subjects with pathologically confirmed frontotemporal lobar degeneration (FTLD). Methods: In this case-control study, we identified all subjects with a pathologic diagnosis of FTLD with TDP-43 immunoreactive inclusions (FTLD-TDP) and at least one volumetric head MRI scan (n = 42). In each case we applied published criteria for subclassification of FTLD-TDP into FTLD-TDP types 1-3. Voxel-based morphometry was used to compare subjects with each of the different FTLD-TDP types to age- and gender-matched normal controls (n = 30). We also assessed different pathologic and genetic variants within, and across, the different types. Results: Twenty-two subjects were classified as FTLD-TDP type 1, 9 as type 2, and 11 as type 3. We identified different patterns of atrophy across the types with type 1 showing frontotemporal and parietal atrophy, type 2 predominantly anterior temporal lobe atrophy, and type 3 predominantly posterior frontal atrophy. Within the FTLD-TDP type 1 group, those with a progranulin mutation had significantly more lateral temporal lobe atrophy than those without. All type 2 subjects were diagnosed with semantic dementia. Subjects with a pathologic diagnosis of FTLD with motor neuron degeneration had a similar pattern of atrophy, regardless of whether they were type 1 or type 3. Conclusions: Although there are different patterns of atrophy across the different FTLD-TDP types, it appears that genetic and pathologic factors may also affect the patterns of atrophy.",
author = "Whitwell, {Jennifer Lynn} and Jack, {Clifford R Jr.} and Parisi, {Joseph E} and Senjem, {M. L.} and Knopman, {David S} and Boeve, {Bradley F} and Rademakers, {Rosa V} and M. Baker and Petersen, {Ronald Carl} and Dickson, {Dennis W} and Josephs, {Keith Anthony}",
year = "2010",
month = "12",
day = "14",
doi = "10.1212/WNL.0b013e31820203c2",
language = "English (US)",
volume = "75",
pages = "2212--2220",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
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}

TY - JOUR

T1 - Does TDP-43 type confer a distinct pattern of atrophy in frontotemporal lobar degeneration?

AU - Whitwell, Jennifer Lynn

AU - Jack, Clifford R Jr.

AU - Parisi, Joseph E

AU - Senjem, M. L.

AU - Knopman, David S

AU - Boeve, Bradley F

AU - Rademakers, Rosa V

AU - Baker, M.

AU - Petersen, Ronald Carl

AU - Dickson, Dennis W

AU - Josephs, Keith Anthony

PY - 2010/12/14

Y1 - 2010/12/14

N2 - Objective: To determine whether TDP-43 type is associated with distinct patterns of brain atrophy on MRI in subjects with pathologically confirmed frontotemporal lobar degeneration (FTLD). Methods: In this case-control study, we identified all subjects with a pathologic diagnosis of FTLD with TDP-43 immunoreactive inclusions (FTLD-TDP) and at least one volumetric head MRI scan (n = 42). In each case we applied published criteria for subclassification of FTLD-TDP into FTLD-TDP types 1-3. Voxel-based morphometry was used to compare subjects with each of the different FTLD-TDP types to age- and gender-matched normal controls (n = 30). We also assessed different pathologic and genetic variants within, and across, the different types. Results: Twenty-two subjects were classified as FTLD-TDP type 1, 9 as type 2, and 11 as type 3. We identified different patterns of atrophy across the types with type 1 showing frontotemporal and parietal atrophy, type 2 predominantly anterior temporal lobe atrophy, and type 3 predominantly posterior frontal atrophy. Within the FTLD-TDP type 1 group, those with a progranulin mutation had significantly more lateral temporal lobe atrophy than those without. All type 2 subjects were diagnosed with semantic dementia. Subjects with a pathologic diagnosis of FTLD with motor neuron degeneration had a similar pattern of atrophy, regardless of whether they were type 1 or type 3. Conclusions: Although there are different patterns of atrophy across the different FTLD-TDP types, it appears that genetic and pathologic factors may also affect the patterns of atrophy.

AB - Objective: To determine whether TDP-43 type is associated with distinct patterns of brain atrophy on MRI in subjects with pathologically confirmed frontotemporal lobar degeneration (FTLD). Methods: In this case-control study, we identified all subjects with a pathologic diagnosis of FTLD with TDP-43 immunoreactive inclusions (FTLD-TDP) and at least one volumetric head MRI scan (n = 42). In each case we applied published criteria for subclassification of FTLD-TDP into FTLD-TDP types 1-3. Voxel-based morphometry was used to compare subjects with each of the different FTLD-TDP types to age- and gender-matched normal controls (n = 30). We also assessed different pathologic and genetic variants within, and across, the different types. Results: Twenty-two subjects were classified as FTLD-TDP type 1, 9 as type 2, and 11 as type 3. We identified different patterns of atrophy across the types with type 1 showing frontotemporal and parietal atrophy, type 2 predominantly anterior temporal lobe atrophy, and type 3 predominantly posterior frontal atrophy. Within the FTLD-TDP type 1 group, those with a progranulin mutation had significantly more lateral temporal lobe atrophy than those without. All type 2 subjects were diagnosed with semantic dementia. Subjects with a pathologic diagnosis of FTLD with motor neuron degeneration had a similar pattern of atrophy, regardless of whether they were type 1 or type 3. Conclusions: Although there are different patterns of atrophy across the different FTLD-TDP types, it appears that genetic and pathologic factors may also affect the patterns of atrophy.

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U2 - 10.1212/WNL.0b013e31820203c2

DO - 10.1212/WNL.0b013e31820203c2

M3 - Article

C2 - 21172844

AN - SCOPUS:78650834063

VL - 75

SP - 2212

EP - 2220

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 24

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