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01-11-2019 | Alzheimer's Disease | Original Paper

Increased prevalence of granulovacuolar degeneration in C9orf72 mutation

Authors: Yuichi Riku, Charles Duyckaerts, Susana Boluda, Isabelle Plu, Isabelle Le Ber, Stéphanie Millecamps, François Salachas, Mari Yoshida, Takashi Ando, Masahisa Katsuno, Gen Sobue, Danielle Seilhean, Brainbank NeuroCEB Neuropathology Network

Published in: Acta Neuropathologica | Issue 5/2019

Abstract

Granulovacuolar degeneration (GVD) is usually found in Alzheimer’s disease (AD) cases or in elderly individuals. Its severity correlates positively with the density of neurofibrillary tangles (NFTs). Mechanisms underlying GVD formation are unknown. We assessed the prevalence and distribution of GVD in cases with TDP-43-related frontotemporal lobar degeneration (FTLD-TDP) and amyotrophic lateral sclerosis (ALS-TDP). Consecutively autopsied cases with FTLD/ALS-TDP and C9orf72 mutations (FTLD/ALS-C9; N = 29), cases with FTLD/ALS-TDP without C9orf72 mutations (FTLD/ALS-nonC9; N = 46), and age-matched healthy controls (N = 40) were studied. The prevalence of GVD was significantly higher in the FTLD/ALS-C9 cases (26/29 cases) than in the FTLD/ALS-nonC9 cases (15/46 cases; Fisher exact test; p < 2×10⁻⁶) or in the control group (12/40 individuals; p < 1×10⁻⁶). Average Braak stages and ages of death were not significantly different among the groups. The CA2 sector was most frequently affected in the FTLD/ALS-C9 group, whereas the CA1/subiculum was the most vulnerable area in the other groups. Extension of GVD correlated with the clinical duration of the disease in the FTLD/ALS-C9 cases but not in the FTLD/ALS-nonC9 cases. The GVD-containing neurons frequently had dipeptide repeat (DPR) protein inclusions. GVD granules labeled with antibodies directed against charged multivesicular body protein 2B or casein kinase 1δ were attached to DPR inclusions within GVD. Our results suggest that development of GVD and DPR inclusions is related to common pathogenic mechanisms and that GVD is not only associated with NFTs seen in AD cases or aging individuals.

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Title: Increased prevalence of granulovacuolar degeneration in C9orf72 mutation
Authors: Yuichi Riku
Charles Duyckaerts
Susana Boluda
Isabelle Plu
Isabelle Le Ber
Stéphanie Millecamps
François Salachas
Mari Yoshida
Takashi Ando
Masahisa Katsuno
Gen Sobue
Danielle Seilhean
Brainbank NeuroCEB Neuropathology Network
Publication date: 01-11-2019
Publisher: Springer Berlin Heidelberg
Keywords: Alzheimer's Disease
Alzheimer's Disease
Published in: Acta Neuropathologica / Issue 5/2019
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-019-02028-6

At a glance: The STEP trials

Springer Medicine

Increased prevalence of granulovacuolar degeneration in C9orf72 mutation

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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