TDP-43 in Alzheimer's disease is not associated with clinical FTLD or Parkinsonism

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Abstract

Widespread deposition of TAR DNA-binding protein of 43 kDa (TDP-43), a major protein inclusion commonly found in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) can also be seen in a subset of cases with Alzheimer's disease (AD). Some of these AD cases have TDP-43 immunoreactivity in basal ganglia (BG) and substantia nigra (SN), regions that when affected can be associated with parkinsonian signs or symptoms, or even features suggestive of frontotemporal dementia. Here, we examined the presence of clinical features of FTLD, parkinsonian signs and symptoms, and BG atrophy on MRI, in 51 pathologically confirmed AD cases (Braak neurofibrillary tangle stage IV-VI) with widespread TDP-43 deposition, with and without BG and SN involvement. All 51 cases had presented with progressive cognitive impairment with prominent memory deficits. None of the patients demonstrated early behavioral disinhibition, apathy, loss of empathy, stereotyped behavior, hyperorality, and/or executive deficits. Furthermore, TDP-43 deposition in BG or SN had no significant association with tremor (p = 0.80), rigidity (p = 0.19), bradykinesia (p = 0.19), and gait/postural instability (p = 0.39). Volumes of the BG structures were not associated with TDP-43 deposition in the BG. The present study demonstrates that TDP-43 deposition in pathologically confirmed AD cases is not associated with a clinical manifestation suggestive of FTLD, or parkinsonian features.

Original languageEnglish (US)
Pages (from-to)1344-1348
Number of pages5
JournalJournal of Neurology
Volume261
Issue number7
DOIs
StatePublished - 2014

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Frontotemporal Lobar Degeneration
Parkinsonian Disorders
Basal Ganglia
Alzheimer Disease
Substantia Nigra
Signs and Symptoms
Stereotyped Behavior
Apathy
Frontotemporal Dementia
Hypokinesia
Neurofibrillary Tangles
Memory Disorders
Amyotrophic Lateral Sclerosis
DNA-Binding Proteins
Tremor
Gait
Atrophy

Keywords

  • Alzheimer's disease
  • Frontotemporal dementia
  • Parkinsonism
  • TDP-43

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Medicine(all)

Cite this

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title = "TDP-43 in Alzheimer's disease is not associated with clinical FTLD or Parkinsonism",
abstract = "Widespread deposition of TAR DNA-binding protein of 43 kDa (TDP-43), a major protein inclusion commonly found in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) can also be seen in a subset of cases with Alzheimer's disease (AD). Some of these AD cases have TDP-43 immunoreactivity in basal ganglia (BG) and substantia nigra (SN), regions that when affected can be associated with parkinsonian signs or symptoms, or even features suggestive of frontotemporal dementia. Here, we examined the presence of clinical features of FTLD, parkinsonian signs and symptoms, and BG atrophy on MRI, in 51 pathologically confirmed AD cases (Braak neurofibrillary tangle stage IV-VI) with widespread TDP-43 deposition, with and without BG and SN involvement. All 51 cases had presented with progressive cognitive impairment with prominent memory deficits. None of the patients demonstrated early behavioral disinhibition, apathy, loss of empathy, stereotyped behavior, hyperorality, and/or executive deficits. Furthermore, TDP-43 deposition in BG or SN had no significant association with tremor (p = 0.80), rigidity (p = 0.19), bradykinesia (p = 0.19), and gait/postural instability (p = 0.39). Volumes of the BG structures were not associated with TDP-43 deposition in the BG. The present study demonstrates that TDP-43 deposition in pathologically confirmed AD cases is not associated with a clinical manifestation suggestive of FTLD, or parkinsonian features.",
keywords = "Alzheimer's disease, Frontotemporal dementia, Parkinsonism, TDP-43",
author = "Youngsin Jung and Dickson, {Dennis W} and Murray, {Melissa E} and Whitwell, {Jennifer Lynn} and Knopman, {David S} and Boeve, {Bradley F} and Jack, {Clifford R Jr.} and Parisi, {Joseph E} and Petersen, {Ronald Carl} and Josephs, {Keith Anthony}",
year = "2014",
doi = "10.1007/s00415-014-7352-5",
language = "English (US)",
volume = "261",
pages = "1344--1348",
journal = "Journal of Neurology",
issn = "0340-5354",
publisher = "D. Steinkopff-Verlag",
number = "7",

}

TY - JOUR

T1 - TDP-43 in Alzheimer's disease is not associated with clinical FTLD or Parkinsonism

AU - Jung, Youngsin

AU - Dickson, Dennis W

AU - Murray, Melissa E

AU - Whitwell, Jennifer Lynn

AU - Knopman, David S

AU - Boeve, Bradley F

AU - Jack, Clifford R Jr.

AU - Parisi, Joseph E

AU - Petersen, Ronald Carl

AU - Josephs, Keith Anthony

PY - 2014

Y1 - 2014

N2 - Widespread deposition of TAR DNA-binding protein of 43 kDa (TDP-43), a major protein inclusion commonly found in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) can also be seen in a subset of cases with Alzheimer's disease (AD). Some of these AD cases have TDP-43 immunoreactivity in basal ganglia (BG) and substantia nigra (SN), regions that when affected can be associated with parkinsonian signs or symptoms, or even features suggestive of frontotemporal dementia. Here, we examined the presence of clinical features of FTLD, parkinsonian signs and symptoms, and BG atrophy on MRI, in 51 pathologically confirmed AD cases (Braak neurofibrillary tangle stage IV-VI) with widespread TDP-43 deposition, with and without BG and SN involvement. All 51 cases had presented with progressive cognitive impairment with prominent memory deficits. None of the patients demonstrated early behavioral disinhibition, apathy, loss of empathy, stereotyped behavior, hyperorality, and/or executive deficits. Furthermore, TDP-43 deposition in BG or SN had no significant association with tremor (p = 0.80), rigidity (p = 0.19), bradykinesia (p = 0.19), and gait/postural instability (p = 0.39). Volumes of the BG structures were not associated with TDP-43 deposition in the BG. The present study demonstrates that TDP-43 deposition in pathologically confirmed AD cases is not associated with a clinical manifestation suggestive of FTLD, or parkinsonian features.

AB - Widespread deposition of TAR DNA-binding protein of 43 kDa (TDP-43), a major protein inclusion commonly found in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) can also be seen in a subset of cases with Alzheimer's disease (AD). Some of these AD cases have TDP-43 immunoreactivity in basal ganglia (BG) and substantia nigra (SN), regions that when affected can be associated with parkinsonian signs or symptoms, or even features suggestive of frontotemporal dementia. Here, we examined the presence of clinical features of FTLD, parkinsonian signs and symptoms, and BG atrophy on MRI, in 51 pathologically confirmed AD cases (Braak neurofibrillary tangle stage IV-VI) with widespread TDP-43 deposition, with and without BG and SN involvement. All 51 cases had presented with progressive cognitive impairment with prominent memory deficits. None of the patients demonstrated early behavioral disinhibition, apathy, loss of empathy, stereotyped behavior, hyperorality, and/or executive deficits. Furthermore, TDP-43 deposition in BG or SN had no significant association with tremor (p = 0.80), rigidity (p = 0.19), bradykinesia (p = 0.19), and gait/postural instability (p = 0.39). Volumes of the BG structures were not associated with TDP-43 deposition in the BG. The present study demonstrates that TDP-43 deposition in pathologically confirmed AD cases is not associated with a clinical manifestation suggestive of FTLD, or parkinsonian features.

KW - Alzheimer's disease

KW - Frontotemporal dementia

KW - Parkinsonism

KW - TDP-43

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U2 - 10.1007/s00415-014-7352-5

DO - 10.1007/s00415-014-7352-5

M3 - Article

C2 - 24760339

AN - SCOPUS:84904876318

VL - 261

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JO - Journal of Neurology

JF - Journal of Neurology

SN - 0340-5354

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