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01-12-2018 | Original Communication

Mixed TDP-43 proteinopathy and tauopathy in frontotemporal lobar degeneration: nine case series

Authors: Eun-Joo Kim, Jesse A. Brown, Jersey Deng, Ji-Hye L. Hwang, Salvatore Spina, Zachary A. Miller, Mary G. DeMay, Victor Valcour, Anna Karydas, Eliana Marisa Ramos, Giovanni Coppola, Bruce L. Miller, Howard J. Rosen, William W. Seeley, Lea T. Grinberg

Published in: Journal of Neurology | Issue 12/2018

Abstract

Objectives

To determine the clinical, anatomical, genetic and pathological features of dual frontotemporal lobar degeneration (FTLD) pathology: FTLD-tau and FTLD-TDP-43 in a large clinicopathological cohort.

Methods

We selected subjects with mixed FTLD-TDP and FTLD-tau from 247 FTLD cases from the University of California, San Francisco, Neurodegenerative Disease Brain Bank collected between 2000 and 2016 and compared their clinical, anatomical, genetic, imaging and pathological signatures with those of subjects with pure FTLD.

Results

We found nine cases (3.6%) with prominent FTLD-TDP and FTLD-tau. Six cases were sporadic, whereas one case had a C9ORF72 expansion, another had a TARDBP A90V variant, and the other had an MAPT p.A152T variant. The subtypes of FTLD-TDP and FTLD-tau varied. Mixed FTLD cases were older and tended to show a higher burden of Alzheimer disease pathology (3/9, 33%). The neuroimaging signature of mixed cases, in general, included more widespread atrophy than that of pure groups. Specifically, cases of mixed corticobasal degeneration (CBD) with FTLD-TDP showed more prominent asymmetric left-sided atrophy than did those of pure CBD. However, the clinical phenotype of mixed cases was similar to that seen in pure FTLD.

Conclusions

Although patients with mixed FTLD-TDP and FTLD-tau are rare, in-depth clinical, pathological and genetic investigations may shed light on the genetic and biochemical pathways that cause the accumulation of multiple proteinaceous inclusions and inform therapeutic targets that may be beneficial to each one of these abnormal protein misfoldings.

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Title: Mixed TDP-43 proteinopathy and tauopathy in frontotemporal lobar degeneration: nine case series
Authors: Eun-Joo Kim
Jesse A. Brown
Jersey Deng
Ji-Hye L. Hwang
Salvatore Spina
Zachary A. Miller
Mary G. DeMay
Victor Valcour
Anna Karydas
Eliana Marisa Ramos
Giovanni Coppola
Bruce L. Miller
Howard J. Rosen
William W. Seeley
Lea T. Grinberg
Publication date: 01-12-2018
Publisher: Springer Berlin Heidelberg
Published in: Journal of Neurology / Issue 12/2018
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-018-9086-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Mixed TDP-43 proteinopathy and tauopathy in frontotemporal lobar degeneration: nine case series

Abstract

Objectives

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objectives

Methods

Results

Conclusions

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