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Fulminant corticobasal degeneration: a distinct variant with predominant neuronal tau aggregates

Authors :
Lea R'Bibo
John C. Hedreen
Matthew Ellis
Gabor G. Kovacs
Kieren Allinson
Sebastian Brandner
Jean Paul Vonsattel
John Hardy
Thomas T. Warner
Eniko Veronika Kovari
Safa Al-Sarraj
David G. Mann
Glenda M. Halliday
Edwin Jabbari
Tamas Revesz
Johannes Attems
Helen Ling
Ellen Gelpi
James W. Ironside
Seth Love
Teisha Bradshaw
Roberto Simone
Rohan de Silva
Karen Davey
Núria Setó-Salvia
Kin Y. Mok
Daniela Hansen
Selina Wray
Janice L. Holton
Zane Jaunmuktane
Huw R. Morris
Ling, Helen [0000-0003-1532-3526]
Revesz, Tamas [0000-0003-2501-0259]
Apollo - University of Cambridge Repository
Source :
Acta Neuropathologica, Acta Neuropathologica, Vol. 139, No 4 (2020) pp. 717-734, Ling, H, Gelpi, E, Davey, K, Jaunmuktane, Z, Mok, K Y, Jabbari, E, Simone, R, R'Bibo, L, Brandner, S, Ellis, M, Attems, J, Mann, D, Halliday, G M, Al-Sarraj, S, Hedreen, J, Ironside, J W, Kovacs, G G, Kovari, E, Love, S, Vonsattel, J P G, Allinson, K S J, Hansen, D, Bradshaw, T, Setó-Salvia, N, Wray, S, de Silva, R, Morris, H R, Warner, T T, Holton, J L & Revesz, T 2020, ' Fulminant corticobasal degeneration : a distinct variant with predominant neuronal tau aggregates ', Acta Neuropathologica . https://doi.org/10.1007/s00401-019-02119-4
Publication Year :
2020
Publisher :
Springer Berlin Heidelberg, 2020.

Abstract

Corticobasal degeneration typically progresses gradually over 5–7 years from onset till death. Fulminant corticobasal degeneration cases with a rapidly progressive course were rarely reported (RP-CBD). This study aimed to investigate their neuropathological characteristics. Of the 124 autopsy-confirmed corticobasal degeneration cases collected from 14 centres, we identified 6 RP-CBD cases (4.8%) who died of advanced disease within 3 years of onset. These RP-CBD cases had different clinical phenotypes including rapid global cognitive decline (N = 2), corticobasal syndrome (N = 2) and Richardson’s syndrome (N = 2). We also studied four corticobasal degeneration cases with an average disease duration of 3 years or less, who died of another unrelated illness (Intermediate-CBD). Finally, we selected 12 age-matched corticobasal degeneration cases out of a cohort of 110, who had a typical gradually progressive course and reached advanced clinical stage (End-stage-CBD). Quantitative analysis showed high overall tau burden (p = 0.2) and severe nigral cell loss (p = 0.47) in both the RP-CBD and End-stage-CBD groups consistent with advanced pathological changes, while the Intermediate-CBD group (mean disease duration = 3 years) had milder changes than End-stage-CBD (p p p = 0.02). In contrast to the predominance of astrocytic plaques we previously reported in preclinical asymptomatic corticobasal degeneration cases, neuronal tau aggregates predominated in RP-CBD exceeding those in Intermediate-CBD (anterior frontal cortex: p p = 0.001) and End-stage-CBD (anterior frontal cortex: p = 0.03, caudate: p = 0.01) as demonstrated by its higher neuronal-to-astrocytic plaque ratios in both anterior frontal cortex and caudate. We did not identify any difference in age at onset, any pathogenic tau mutation or concomitant pathologies that could have contributed to the rapid progression of these RP-CBD cases. Mild TDP-43 pathology was observed in three RP-CBD cases. All RP-CBD cases were men. The MAPT H2 haplotype, known to be protective, was identified in one RP-CBD case (17%) and 8 of the matched End-stage-CBD cases (67%). We conclude that RP-CBD is a distinct aggressive variant of corticobasal degeneration with characteristic neuropathological substrates resulting in a fulminant disease process as evident both clinically and pathologically. Biological factors such as genetic modifiers likely play a pivotal role in the RP-CBD variant and should be the subject of future research.

Details

ISSN :
00016322
Database :
OpenAIRE
Journal :
Acta Neuropathologica, Acta Neuropathologica, Vol. 139, No 4 (2020) pp. 717-734, Ling, H, Gelpi, E, Davey, K, Jaunmuktane, Z, Mok, K Y, Jabbari, E, Simone, R, R'Bibo, L, Brandner, S, Ellis, M, Attems, J, Mann, D, Halliday, G M, Al-Sarraj, S, Hedreen, J, Ironside, J W, Kovacs, G G, Kovari, E, Love, S, Vonsattel, J P G, Allinson, K S J, Hansen, D, Bradshaw, T, Setó-Salvia, N, Wray, S, de Silva, R, Morris, H R, Warner, T T, Holton, J L & Revesz, T 2020, ' Fulminant corticobasal degeneration : a distinct variant with predominant neuronal tau aggregates ', Acta Neuropathologica . https://doi.org/10.1007/s00401-019-02119-4
Accession number :
edsair.doi.dedup.....1c27e8e4743c2dd085f3d550f52436fb