Home > Research > Publications & Outputs > TDP-43 pathological changes in early onset fami...

Research

Associated organisational unit

Links

Text available via DOI:

Keywords

View graph of relations

TDP-43 pathological changes in early onset familial and sporadic Alzheimer's disease, late onset Alzheimer's disease and Down's Syndrome: association with age, hippocampal sclerosis and clinical phenotype

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Published

Standard

TDP-43 pathological changes in early onset familial and sporadic Alzheimer's disease, late onset Alzheimer's disease and Down's Syndrome: association with age, hippocampal sclerosis and clinical phenotype. / Davidson, Yvonne S; Raby, Samantha; Foulds, Penny et al.
In: Acta Neuropathologica, Vol. 122, No. 6, 12.2011, p. 703-713.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Davidson, YS, Raby, S, Foulds, P, Robinson, A, Thompson, JC, Sikkink, S, Yusuf, I, Amin, H, Duplessis, D, Troakes, C, Al-Sarraj, S, Sloan, C, Esiri, MM, Prasher, VP, Allsop, D, Neary, D, Pickering-Brown, SM, Snowden, JS & Mann, DMA 2011, 'TDP-43 pathological changes in early onset familial and sporadic Alzheimer's disease, late onset Alzheimer's disease and Down's Syndrome: association with age, hippocampal sclerosis and clinical phenotype', Acta Neuropathologica, vol. 122, no. 6, pp. 703-713. https://doi.org/10.1007/s00401-011-0879-y

APA

Davidson, Y. S., Raby, S., Foulds, P., Robinson, A., Thompson, J. C., Sikkink, S., Yusuf, I., Amin, H., Duplessis, D., Troakes, C., Al-Sarraj, S., Sloan, C., Esiri, M. M., Prasher, V. P., Allsop, D., Neary, D., Pickering-Brown, S. M., Snowden, J. S., & Mann, D. M. A. (2011). TDP-43 pathological changes in early onset familial and sporadic Alzheimer's disease, late onset Alzheimer's disease and Down's Syndrome: association with age, hippocampal sclerosis and clinical phenotype. Acta Neuropathologica, 122(6), 703-713. https://doi.org/10.1007/s00401-011-0879-y

Vancouver

Davidson YS, Raby S, Foulds P, Robinson A, Thompson JC, Sikkink S et al. TDP-43 pathological changes in early onset familial and sporadic Alzheimer's disease, late onset Alzheimer's disease and Down's Syndrome: association with age, hippocampal sclerosis and clinical phenotype. Acta Neuropathologica. 2011 Dec;122(6):703-713. Epub 2011 Oct 4. doi: 10.1007/s00401-011-0879-y

Author

Davidson, Yvonne S ; Raby, Samantha ; Foulds, Penny et al. / TDP-43 pathological changes in early onset familial and sporadic Alzheimer's disease, late onset Alzheimer's disease and Down's Syndrome : association with age, hippocampal sclerosis and clinical phenotype. In: Acta Neuropathologica. 2011 ; Vol. 122, No. 6. pp. 703-713.

Bibtex

@article{6474dd63890a439497827795dbcc4c06,
title = "TDP-43 pathological changes in early onset familial and sporadic Alzheimer's disease, late onset Alzheimer's disease and Down's Syndrome: association with age, hippocampal sclerosis and clinical phenotype",
abstract = "TDP-43 immunoreactive (TDP-43-ir) pathological changes were investigated in the temporal cortex and hippocampus of 11 patients with autosomal dominant familial forms of Alzheimer{\textquoteright}s disease (FAD), 169 patients with sporadic AD [85 with early onset disease (EOAD) (i.e before 65 years of age), and 84 with late onset after this age (LOAD)], 50 individuals with Down{\textquoteright}s Syndrome (DS) and 5 patients with primary hippocampal sclerosis (HS). TDP-43-ir pathological changes were present, overall, in 34/180 of AD cases. They were present in 1/11 (9%) FAD, and 9/85 (10%) EOAD patients but were significantly more common (p = 0.003) in LOAD where 24/84 (29%) patients showed such changes. There were no demographic differences, other than onset age, between AD patients with or without TDP-43-ir pathological changes. Double immunolabelling indicated that these TDP-43-ir inclusions were frequently ubiquitinated, but were only rarely AT8 (tau) immunoreactive. Only 3 elderly DS individuals and 4/5 cases of primary HS showed similar changes. Overall, 21.7% of AD cases and 6% DS cases showed hippocampal sclerosis (HS). However, only 9% FAD cases and 16% EOAD cases showed HS, but 29% LOAD cases showed HS. The proportion of EOAD cases with both TDP-43 pathology and HS tended to be greater than those in LOAD, where nearly half of all the cases with TDP-43 pathology did not show HS. The presence of TDP-43-ir changes in AD and DS may therefore be a secondary phenomenon, relating more to ageing than to AD itself. Nevertheless, a challenge to such an interpretation comes from the finding in AD of a strong relationship between TDP-43 pathology and cognitive phenotype. Patients with TDP-43 pathology were significantly more likely to present with an amnestic syndrome than those without (p < 0.0001), in keeping with pathological changes in medial temporal lobe structures. HS was also associated more commonly with an amnestic presentation (p < 0.005), but this association disappeared when TDP-43-positive cases were excluded from the analysis. TDP-43 may, after all, be integral to the pathology of AD, and to some extent determine the clinical phenotype present.",
keywords = "Alzheimer{\textquoteright}s disease , Down{\textquoteright}s syndrome , TDP-43 , Hippocampal sclerosis",
author = "Davidson, {Yvonne S} and Samantha Raby and Penny Foulds and Andrew Robinson and Thompson, {Jennifer C} and Stephen Sikkink and Imran Yusuf and Hanan Amin and Daniel Duplessis and Claire Troakes and Safa Al-Sarraj and Carolyn Sloan and Esiri, {Margaret M} and Prasher, {Vee P} and David Allsop and David Neary and Pickering-Brown, {Stuart M} and Snowden, {Julie S} and Mann, {David M A}",
year = "2011",
month = dec,
doi = "10.1007/s00401-011-0879-y",
language = "English",
volume = "122",
pages = "703--713",
journal = "Acta Neuropathologica",
issn = "0001-6322",
publisher = "Springer Verlag",
number = "6",

}

RIS

TY - JOUR

T1 - TDP-43 pathological changes in early onset familial and sporadic Alzheimer's disease, late onset Alzheimer's disease and Down's Syndrome

T2 - association with age, hippocampal sclerosis and clinical phenotype

AU - Davidson, Yvonne S

AU - Raby, Samantha

AU - Foulds, Penny

AU - Robinson, Andrew

AU - Thompson, Jennifer C

AU - Sikkink, Stephen

AU - Yusuf, Imran

AU - Amin, Hanan

AU - Duplessis, Daniel

AU - Troakes, Claire

AU - Al-Sarraj, Safa

AU - Sloan, Carolyn

AU - Esiri, Margaret M

AU - Prasher, Vee P

AU - Allsop, David

AU - Neary, David

AU - Pickering-Brown, Stuart M

AU - Snowden, Julie S

AU - Mann, David M A

PY - 2011/12

Y1 - 2011/12

N2 - TDP-43 immunoreactive (TDP-43-ir) pathological changes were investigated in the temporal cortex and hippocampus of 11 patients with autosomal dominant familial forms of Alzheimer’s disease (FAD), 169 patients with sporadic AD [85 with early onset disease (EOAD) (i.e before 65 years of age), and 84 with late onset after this age (LOAD)], 50 individuals with Down’s Syndrome (DS) and 5 patients with primary hippocampal sclerosis (HS). TDP-43-ir pathological changes were present, overall, in 34/180 of AD cases. They were present in 1/11 (9%) FAD, and 9/85 (10%) EOAD patients but were significantly more common (p = 0.003) in LOAD where 24/84 (29%) patients showed such changes. There were no demographic differences, other than onset age, between AD patients with or without TDP-43-ir pathological changes. Double immunolabelling indicated that these TDP-43-ir inclusions were frequently ubiquitinated, but were only rarely AT8 (tau) immunoreactive. Only 3 elderly DS individuals and 4/5 cases of primary HS showed similar changes. Overall, 21.7% of AD cases and 6% DS cases showed hippocampal sclerosis (HS). However, only 9% FAD cases and 16% EOAD cases showed HS, but 29% LOAD cases showed HS. The proportion of EOAD cases with both TDP-43 pathology and HS tended to be greater than those in LOAD, where nearly half of all the cases with TDP-43 pathology did not show HS. The presence of TDP-43-ir changes in AD and DS may therefore be a secondary phenomenon, relating more to ageing than to AD itself. Nevertheless, a challenge to such an interpretation comes from the finding in AD of a strong relationship between TDP-43 pathology and cognitive phenotype. Patients with TDP-43 pathology were significantly more likely to present with an amnestic syndrome than those without (p < 0.0001), in keeping with pathological changes in medial temporal lobe structures. HS was also associated more commonly with an amnestic presentation (p < 0.005), but this association disappeared when TDP-43-positive cases were excluded from the analysis. TDP-43 may, after all, be integral to the pathology of AD, and to some extent determine the clinical phenotype present.

AB - TDP-43 immunoreactive (TDP-43-ir) pathological changes were investigated in the temporal cortex and hippocampus of 11 patients with autosomal dominant familial forms of Alzheimer’s disease (FAD), 169 patients with sporadic AD [85 with early onset disease (EOAD) (i.e before 65 years of age), and 84 with late onset after this age (LOAD)], 50 individuals with Down’s Syndrome (DS) and 5 patients with primary hippocampal sclerosis (HS). TDP-43-ir pathological changes were present, overall, in 34/180 of AD cases. They were present in 1/11 (9%) FAD, and 9/85 (10%) EOAD patients but were significantly more common (p = 0.003) in LOAD where 24/84 (29%) patients showed such changes. There were no demographic differences, other than onset age, between AD patients with or without TDP-43-ir pathological changes. Double immunolabelling indicated that these TDP-43-ir inclusions were frequently ubiquitinated, but were only rarely AT8 (tau) immunoreactive. Only 3 elderly DS individuals and 4/5 cases of primary HS showed similar changes. Overall, 21.7% of AD cases and 6% DS cases showed hippocampal sclerosis (HS). However, only 9% FAD cases and 16% EOAD cases showed HS, but 29% LOAD cases showed HS. The proportion of EOAD cases with both TDP-43 pathology and HS tended to be greater than those in LOAD, where nearly half of all the cases with TDP-43 pathology did not show HS. The presence of TDP-43-ir changes in AD and DS may therefore be a secondary phenomenon, relating more to ageing than to AD itself. Nevertheless, a challenge to such an interpretation comes from the finding in AD of a strong relationship between TDP-43 pathology and cognitive phenotype. Patients with TDP-43 pathology were significantly more likely to present with an amnestic syndrome than those without (p < 0.0001), in keeping with pathological changes in medial temporal lobe structures. HS was also associated more commonly with an amnestic presentation (p < 0.005), but this association disappeared when TDP-43-positive cases were excluded from the analysis. TDP-43 may, after all, be integral to the pathology of AD, and to some extent determine the clinical phenotype present.

KW - Alzheimer’s disease

KW - Down’s syndrome

KW - TDP-43

KW - Hippocampal sclerosis

U2 - 10.1007/s00401-011-0879-y

DO - 10.1007/s00401-011-0879-y

M3 - Journal article

C2 - 21968532

VL - 122

SP - 703

EP - 713

JO - Acta Neuropathologica

JF - Acta Neuropathologica

SN - 0001-6322

IS - 6

ER -