Comparison of extent of tau pathology in patients with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), frontotemporal lobar degeneration with Pick bodies and early onset Alzheimer's disease

A. M. Shiarli, R. Jennings, J. Shi, K. Bailey, Y. Davidson, J. Tian, E. H. Bigio, B. Ghetti, J. R. Murrell, M. B. Delisle, S. Mirra, B. Crain, P. Zolo, K. Arima, E. Iseki, S. Murayama, H. Kretzschmar, M. Neumann, C. Lippa, G. HallidayJ. MacKenzie, N. Khan, R. Ravid, Dennis W Dickson, Zbigniew K Wszolek, T. Iwatsubo, S. M. Pickering-Brown, D. M A Mann

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

In order to gain insight into the pathogenesis of frontotemporal lobar degeneration (FTLD), the mean tau load in frontal cortex was compared in 34 patients with frontotemporal dementia linked to chromosome 17 (FTDP-17) with 12 different mutations in the tau gene (MAPT), 11 patients with sporadic FTLD with Pick bodies and 25 patients with early onset Alzheimer's disease (EOAD). Tau load was determined, as percentage of tissue occupied by stained product, by image analysis of immunohistochemically stained sections using the phospho-dependent antibodies AT8, AT100 and AT180. With AT8 and AT180 antibodies, the amount of tau was significantly (P < 0.001 in each instance) less than that in EOAD for both FTDP-17 (8.5% and 10.0% respectively) and sporadic FTLD with Pick bodies (16.1% and 10.0% respectively). With AT100, the amount of tau detected in FTDP-17 was 54% (P < 0.001) of that detected in EOAD, but no tau was detected in sporadic FTLD with Pick bodies using this particular antibody. The amount of insoluble tau deposited within the brain in FTDP-17 did not depend in any systematic way upon where the MAPT mutation was topographically located within the gene, or on the physiological or structural change generated by the mutation, regardless of which anti-tau antibody was used. Not only does the amount of tau deposited in the brain differ between the three disorders, but the pattern of phosphorylation of tau also varies according to disease. These findings raise important questions relating to the role of aggregated tau in neurodegeneration - whether this represents an adaptive response which promotes the survival of neurones, or whether it is a detrimental change that directly, or indirectly, brings about the demize of the affected cell.

Original languageEnglish (US)
Pages (from-to)374-387
Number of pages14
JournalNeuropathology and Applied Neurobiology
Volume32
Issue number4
DOIs
StatePublished - Aug 2006

Fingerprint

Frontotemporal Lobar Degeneration
Frontotemporal Dementia
Chromosomes, Human, Pair 17
Alzheimer Disease
Pathology
Mutation
Antibodies
Brain
Frontal Lobe
Genes
Anti-Idiotypic Antibodies
Phosphorylation
Neurons

Keywords

  • Alzheimer's disease
  • Frontotemporal lobar degeneration
  • Neurofibrillary tangle
  • Pick bodies
  • Tau gene
  • Tau protein

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Comparison of extent of tau pathology in patients with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), frontotemporal lobar degeneration with Pick bodies and early onset Alzheimer's disease. / Shiarli, A. M.; Jennings, R.; Shi, J.; Bailey, K.; Davidson, Y.; Tian, J.; Bigio, E. H.; Ghetti, B.; Murrell, J. R.; Delisle, M. B.; Mirra, S.; Crain, B.; Zolo, P.; Arima, K.; Iseki, E.; Murayama, S.; Kretzschmar, H.; Neumann, M.; Lippa, C.; Halliday, G.; MacKenzie, J.; Khan, N.; Ravid, R.; Dickson, Dennis W; Wszolek, Zbigniew K; Iwatsubo, T.; Pickering-Brown, S. M.; Mann, D. M A.

In: Neuropathology and Applied Neurobiology, Vol. 32, No. 4, 08.2006, p. 374-387.

Research output: Contribution to journalArticle

Shiarli, AM, Jennings, R, Shi, J, Bailey, K, Davidson, Y, Tian, J, Bigio, EH, Ghetti, B, Murrell, JR, Delisle, MB, Mirra, S, Crain, B, Zolo, P, Arima, K, Iseki, E, Murayama, S, Kretzschmar, H, Neumann, M, Lippa, C, Halliday, G, MacKenzie, J, Khan, N, Ravid, R, Dickson, DW, Wszolek, ZK, Iwatsubo, T, Pickering-Brown, SM & Mann, DMA 2006, 'Comparison of extent of tau pathology in patients with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), frontotemporal lobar degeneration with Pick bodies and early onset Alzheimer's disease', Neuropathology and Applied Neurobiology, vol. 32, no. 4, pp. 374-387. https://doi.org/10.1111/j.1365-2990.2006.00736.x
Shiarli, A. M. ; Jennings, R. ; Shi, J. ; Bailey, K. ; Davidson, Y. ; Tian, J. ; Bigio, E. H. ; Ghetti, B. ; Murrell, J. R. ; Delisle, M. B. ; Mirra, S. ; Crain, B. ; Zolo, P. ; Arima, K. ; Iseki, E. ; Murayama, S. ; Kretzschmar, H. ; Neumann, M. ; Lippa, C. ; Halliday, G. ; MacKenzie, J. ; Khan, N. ; Ravid, R. ; Dickson, Dennis W ; Wszolek, Zbigniew K ; Iwatsubo, T. ; Pickering-Brown, S. M. ; Mann, D. M A. / Comparison of extent of tau pathology in patients with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), frontotemporal lobar degeneration with Pick bodies and early onset Alzheimer's disease. In: Neuropathology and Applied Neurobiology. 2006 ; Vol. 32, No. 4. pp. 374-387.
@article{b9fbc9ec2fc148ada41e47829f6df24c,
title = "Comparison of extent of tau pathology in patients with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), frontotemporal lobar degeneration with Pick bodies and early onset Alzheimer's disease",
abstract = "In order to gain insight into the pathogenesis of frontotemporal lobar degeneration (FTLD), the mean tau load in frontal cortex was compared in 34 patients with frontotemporal dementia linked to chromosome 17 (FTDP-17) with 12 different mutations in the tau gene (MAPT), 11 patients with sporadic FTLD with Pick bodies and 25 patients with early onset Alzheimer's disease (EOAD). Tau load was determined, as percentage of tissue occupied by stained product, by image analysis of immunohistochemically stained sections using the phospho-dependent antibodies AT8, AT100 and AT180. With AT8 and AT180 antibodies, the amount of tau was significantly (P < 0.001 in each instance) less than that in EOAD for both FTDP-17 (8.5{\%} and 10.0{\%} respectively) and sporadic FTLD with Pick bodies (16.1{\%} and 10.0{\%} respectively). With AT100, the amount of tau detected in FTDP-17 was 54{\%} (P < 0.001) of that detected in EOAD, but no tau was detected in sporadic FTLD with Pick bodies using this particular antibody. The amount of insoluble tau deposited within the brain in FTDP-17 did not depend in any systematic way upon where the MAPT mutation was topographically located within the gene, or on the physiological or structural change generated by the mutation, regardless of which anti-tau antibody was used. Not only does the amount of tau deposited in the brain differ between the three disorders, but the pattern of phosphorylation of tau also varies according to disease. These findings raise important questions relating to the role of aggregated tau in neurodegeneration - whether this represents an adaptive response which promotes the survival of neurones, or whether it is a detrimental change that directly, or indirectly, brings about the demize of the affected cell.",
keywords = "Alzheimer's disease, Frontotemporal lobar degeneration, Neurofibrillary tangle, Pick bodies, Tau gene, Tau protein",
author = "Shiarli, {A. M.} and R. Jennings and J. Shi and K. Bailey and Y. Davidson and J. Tian and Bigio, {E. H.} and B. Ghetti and Murrell, {J. R.} and Delisle, {M. B.} and S. Mirra and B. Crain and P. Zolo and K. Arima and E. Iseki and S. Murayama and H. Kretzschmar and M. Neumann and C. Lippa and G. Halliday and J. MacKenzie and N. Khan and R. Ravid and Dickson, {Dennis W} and Wszolek, {Zbigniew K} and T. Iwatsubo and Pickering-Brown, {S. M.} and Mann, {D. M A}",
year = "2006",
month = "8",
doi = "10.1111/j.1365-2990.2006.00736.x",
language = "English (US)",
volume = "32",
pages = "374--387",
journal = "Neuropathology and Applied Neurobiology",
issn = "0305-1846",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Comparison of extent of tau pathology in patients with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), frontotemporal lobar degeneration with Pick bodies and early onset Alzheimer's disease

AU - Shiarli, A. M.

AU - Jennings, R.

AU - Shi, J.

AU - Bailey, K.

AU - Davidson, Y.

AU - Tian, J.

AU - Bigio, E. H.

AU - Ghetti, B.

AU - Murrell, J. R.

AU - Delisle, M. B.

AU - Mirra, S.

AU - Crain, B.

AU - Zolo, P.

AU - Arima, K.

AU - Iseki, E.

AU - Murayama, S.

AU - Kretzschmar, H.

AU - Neumann, M.

AU - Lippa, C.

AU - Halliday, G.

AU - MacKenzie, J.

AU - Khan, N.

AU - Ravid, R.

AU - Dickson, Dennis W

AU - Wszolek, Zbigniew K

AU - Iwatsubo, T.

AU - Pickering-Brown, S. M.

AU - Mann, D. M A

PY - 2006/8

Y1 - 2006/8

N2 - In order to gain insight into the pathogenesis of frontotemporal lobar degeneration (FTLD), the mean tau load in frontal cortex was compared in 34 patients with frontotemporal dementia linked to chromosome 17 (FTDP-17) with 12 different mutations in the tau gene (MAPT), 11 patients with sporadic FTLD with Pick bodies and 25 patients with early onset Alzheimer's disease (EOAD). Tau load was determined, as percentage of tissue occupied by stained product, by image analysis of immunohistochemically stained sections using the phospho-dependent antibodies AT8, AT100 and AT180. With AT8 and AT180 antibodies, the amount of tau was significantly (P < 0.001 in each instance) less than that in EOAD for both FTDP-17 (8.5% and 10.0% respectively) and sporadic FTLD with Pick bodies (16.1% and 10.0% respectively). With AT100, the amount of tau detected in FTDP-17 was 54% (P < 0.001) of that detected in EOAD, but no tau was detected in sporadic FTLD with Pick bodies using this particular antibody. The amount of insoluble tau deposited within the brain in FTDP-17 did not depend in any systematic way upon where the MAPT mutation was topographically located within the gene, or on the physiological or structural change generated by the mutation, regardless of which anti-tau antibody was used. Not only does the amount of tau deposited in the brain differ between the three disorders, but the pattern of phosphorylation of tau also varies according to disease. These findings raise important questions relating to the role of aggregated tau in neurodegeneration - whether this represents an adaptive response which promotes the survival of neurones, or whether it is a detrimental change that directly, or indirectly, brings about the demize of the affected cell.

AB - In order to gain insight into the pathogenesis of frontotemporal lobar degeneration (FTLD), the mean tau load in frontal cortex was compared in 34 patients with frontotemporal dementia linked to chromosome 17 (FTDP-17) with 12 different mutations in the tau gene (MAPT), 11 patients with sporadic FTLD with Pick bodies and 25 patients with early onset Alzheimer's disease (EOAD). Tau load was determined, as percentage of tissue occupied by stained product, by image analysis of immunohistochemically stained sections using the phospho-dependent antibodies AT8, AT100 and AT180. With AT8 and AT180 antibodies, the amount of tau was significantly (P < 0.001 in each instance) less than that in EOAD for both FTDP-17 (8.5% and 10.0% respectively) and sporadic FTLD with Pick bodies (16.1% and 10.0% respectively). With AT100, the amount of tau detected in FTDP-17 was 54% (P < 0.001) of that detected in EOAD, but no tau was detected in sporadic FTLD with Pick bodies using this particular antibody. The amount of insoluble tau deposited within the brain in FTDP-17 did not depend in any systematic way upon where the MAPT mutation was topographically located within the gene, or on the physiological or structural change generated by the mutation, regardless of which anti-tau antibody was used. Not only does the amount of tau deposited in the brain differ between the three disorders, but the pattern of phosphorylation of tau also varies according to disease. These findings raise important questions relating to the role of aggregated tau in neurodegeneration - whether this represents an adaptive response which promotes the survival of neurones, or whether it is a detrimental change that directly, or indirectly, brings about the demize of the affected cell.

KW - Alzheimer's disease

KW - Frontotemporal lobar degeneration

KW - Neurofibrillary tangle

KW - Pick bodies

KW - Tau gene

KW - Tau protein

UR - http://www.scopus.com/inward/record.url?scp=33745748889&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745748889&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2990.2006.00736.x

DO - 10.1111/j.1365-2990.2006.00736.x

M3 - Article

C2 - 16866983

AN - SCOPUS:33745748889

VL - 32

SP - 374

EP - 387

JO - Neuropathology and Applied Neurobiology

JF - Neuropathology and Applied Neurobiology

SN - 0305-1846

IS - 4

ER -