TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease

Catalina Amador-Ortiz, Wen Lang Lin, Zeshan Ahmed, David Personett, Peter Davies, Ranjan Duara, Neill R. Graff-Radford, Michael L. Hutton, Dennis W. Dickson

Research output: Contribution to journalArticle

483 Citations (Scopus)

Abstract

Objective: This study aimed to determine the frequency of frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) in the setting of hippocampal sclerosis (HpScl) and Alzheimer's disease (AD) using immunohistochemistry for TAR DNA binding protein 43 (TDP-43), a putative marker for FTLD-U. Methods: Initially, 21 cases of HpScl associated with a variety of other pathological processes and 74 cases of AD were screened for FTLD-U with TDP-43 immunohistochemistry. A confirmation study was performed on 93 additional AD cases. Specificity of TDP-43 antibodies was assessed using double-immunolabeling confocal microscopy, immunoelectron microscopy, and biochemistry. Results: TDP-43 immunoreactivity was detected in 71% of HpScl and 23% of AD cases. Double immunostaining of AD cases for TDP-43 and phospho-tau showed that the TDP-43-immunoreactive inclusions were usually distinct from neurofibrillary tangles. At the ultrastructural level, TDP-43 immunoreactivity in AD was associated with granular and filamentous cytosolic material and only occasionally associated with tau filaments. Western blots of AD cases showed a band that migrated at a higher molecular weight than normal TDP-43 that was not present in AD cases without TDP-43 immunoreactivity. Interpretation: These results suggest that as many as 20% of AD cases and more than 70% of HpScl cases have pathology similar to that found in FTLD-U. Whether this represents concomitant FTLD-U or is analogous to colocalization of α-synuclein and tau in AD, reflecting a propensity for codeposition of abnormal protein conformers, remains to be determined.

Original languageEnglish
Pages (from-to)435-445
Number of pages11
JournalAnnals of Neurology
Volume61
Issue number5
DOIs
StatePublished - May 1 2007
Externally publishedYes

Fingerprint

DNA-Binding Proteins
Sclerosis
Alzheimer Disease
Frontotemporal Lobar Degeneration
Synucleins
Immunohistochemistry
Neurofibrillary Tangles
Immunoelectron Microscopy
Pathologic Processes
Confocal Microscopy
Biochemistry
Molecular Weight
Western Blotting
Pathology
Antibodies

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Amador-Ortiz, C., Lin, W. L., Ahmed, Z., Personett, D., Davies, P., Duara, R., ... Dickson, D. W. (2007). TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease. Annals of Neurology, 61(5), 435-445. https://doi.org/10.1002/ana.21154

TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease. / Amador-Ortiz, Catalina; Lin, Wen Lang; Ahmed, Zeshan; Personett, David; Davies, Peter; Duara, Ranjan; Graff-Radford, Neill R.; Hutton, Michael L.; Dickson, Dennis W.

In: Annals of Neurology, Vol. 61, No. 5, 01.05.2007, p. 435-445.

Research output: Contribution to journalArticle

Amador-Ortiz, C, Lin, WL, Ahmed, Z, Personett, D, Davies, P, Duara, R, Graff-Radford, NR, Hutton, ML & Dickson, DW 2007, 'TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease', Annals of Neurology, vol. 61, no. 5, pp. 435-445. https://doi.org/10.1002/ana.21154
Amador-Ortiz C, Lin WL, Ahmed Z, Personett D, Davies P, Duara R et al. TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease. Annals of Neurology. 2007 May 1;61(5):435-445. https://doi.org/10.1002/ana.21154
Amador-Ortiz, Catalina ; Lin, Wen Lang ; Ahmed, Zeshan ; Personett, David ; Davies, Peter ; Duara, Ranjan ; Graff-Radford, Neill R. ; Hutton, Michael L. ; Dickson, Dennis W. / TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease. In: Annals of Neurology. 2007 ; Vol. 61, No. 5. pp. 435-445.
@article{1dcf9024f6304d559ca81c54d475e2f0,
title = "TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease",
abstract = "Objective: This study aimed to determine the frequency of frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) in the setting of hippocampal sclerosis (HpScl) and Alzheimer's disease (AD) using immunohistochemistry for TAR DNA binding protein 43 (TDP-43), a putative marker for FTLD-U. Methods: Initially, 21 cases of HpScl associated with a variety of other pathological processes and 74 cases of AD were screened for FTLD-U with TDP-43 immunohistochemistry. A confirmation study was performed on 93 additional AD cases. Specificity of TDP-43 antibodies was assessed using double-immunolabeling confocal microscopy, immunoelectron microscopy, and biochemistry. Results: TDP-43 immunoreactivity was detected in 71{\%} of HpScl and 23{\%} of AD cases. Double immunostaining of AD cases for TDP-43 and phospho-tau showed that the TDP-43-immunoreactive inclusions were usually distinct from neurofibrillary tangles. At the ultrastructural level, TDP-43 immunoreactivity in AD was associated with granular and filamentous cytosolic material and only occasionally associated with tau filaments. Western blots of AD cases showed a band that migrated at a higher molecular weight than normal TDP-43 that was not present in AD cases without TDP-43 immunoreactivity. Interpretation: These results suggest that as many as 20{\%} of AD cases and more than 70{\%} of HpScl cases have pathology similar to that found in FTLD-U. Whether this represents concomitant FTLD-U or is analogous to colocalization of α-synuclein and tau in AD, reflecting a propensity for codeposition of abnormal protein conformers, remains to be determined.",
author = "Catalina Amador-Ortiz and Lin, {Wen Lang} and Zeshan Ahmed and David Personett and Peter Davies and Ranjan Duara and Graff-Radford, {Neill R.} and Hutton, {Michael L.} and Dickson, {Dennis W.}",
year = "2007",
month = "5",
day = "1",
doi = "10.1002/ana.21154",
language = "English",
volume = "61",
pages = "435--445",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

TY - JOUR

T1 - TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease

AU - Amador-Ortiz, Catalina

AU - Lin, Wen Lang

AU - Ahmed, Zeshan

AU - Personett, David

AU - Davies, Peter

AU - Duara, Ranjan

AU - Graff-Radford, Neill R.

AU - Hutton, Michael L.

AU - Dickson, Dennis W.

PY - 2007/5/1

Y1 - 2007/5/1

N2 - Objective: This study aimed to determine the frequency of frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) in the setting of hippocampal sclerosis (HpScl) and Alzheimer's disease (AD) using immunohistochemistry for TAR DNA binding protein 43 (TDP-43), a putative marker for FTLD-U. Methods: Initially, 21 cases of HpScl associated with a variety of other pathological processes and 74 cases of AD were screened for FTLD-U with TDP-43 immunohistochemistry. A confirmation study was performed on 93 additional AD cases. Specificity of TDP-43 antibodies was assessed using double-immunolabeling confocal microscopy, immunoelectron microscopy, and biochemistry. Results: TDP-43 immunoreactivity was detected in 71% of HpScl and 23% of AD cases. Double immunostaining of AD cases for TDP-43 and phospho-tau showed that the TDP-43-immunoreactive inclusions were usually distinct from neurofibrillary tangles. At the ultrastructural level, TDP-43 immunoreactivity in AD was associated with granular and filamentous cytosolic material and only occasionally associated with tau filaments. Western blots of AD cases showed a band that migrated at a higher molecular weight than normal TDP-43 that was not present in AD cases without TDP-43 immunoreactivity. Interpretation: These results suggest that as many as 20% of AD cases and more than 70% of HpScl cases have pathology similar to that found in FTLD-U. Whether this represents concomitant FTLD-U or is analogous to colocalization of α-synuclein and tau in AD, reflecting a propensity for codeposition of abnormal protein conformers, remains to be determined.

AB - Objective: This study aimed to determine the frequency of frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) in the setting of hippocampal sclerosis (HpScl) and Alzheimer's disease (AD) using immunohistochemistry for TAR DNA binding protein 43 (TDP-43), a putative marker for FTLD-U. Methods: Initially, 21 cases of HpScl associated with a variety of other pathological processes and 74 cases of AD were screened for FTLD-U with TDP-43 immunohistochemistry. A confirmation study was performed on 93 additional AD cases. Specificity of TDP-43 antibodies was assessed using double-immunolabeling confocal microscopy, immunoelectron microscopy, and biochemistry. Results: TDP-43 immunoreactivity was detected in 71% of HpScl and 23% of AD cases. Double immunostaining of AD cases for TDP-43 and phospho-tau showed that the TDP-43-immunoreactive inclusions were usually distinct from neurofibrillary tangles. At the ultrastructural level, TDP-43 immunoreactivity in AD was associated with granular and filamentous cytosolic material and only occasionally associated with tau filaments. Western blots of AD cases showed a band that migrated at a higher molecular weight than normal TDP-43 that was not present in AD cases without TDP-43 immunoreactivity. Interpretation: These results suggest that as many as 20% of AD cases and more than 70% of HpScl cases have pathology similar to that found in FTLD-U. Whether this represents concomitant FTLD-U or is analogous to colocalization of α-synuclein and tau in AD, reflecting a propensity for codeposition of abnormal protein conformers, remains to be determined.

UR - http://www.scopus.com/inward/record.url?scp=34249949338&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34249949338&partnerID=8YFLogxK

U2 - 10.1002/ana.21154

DO - 10.1002/ana.21154

M3 - Article

VL - 61

SP - 435

EP - 445

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 5

ER -