TY  - JOUR
AU  - Davidson, Yvonne S
AU  - Flood, Louis
AU  - Robinson, Andrew C
AU  - Nihei, Yoshihiro
AU  - Mori, Kohji
AU  - Rollinson, Sara
AU  - Richardson, Anna
AU  - Benson, Bridget C
AU  - Jones, Matthew
AU  - Snowden, Julie S
AU  - Pickering-Brown, Stuart
AU  - Haass, Christian
AU  - Lashley, Tammaryn
AU  - Mann, David M A
TI  - Heterogeneous ribonuclear protein A3 (hnRNP A3) is present in dipeptide repeat protein containing inclusions in Frontotemporal Lobar Degeneration and Motor Neurone disease associated with expansions in C9orf72 gene.
JO  - Acta Neuropathologica Communications
VL  - 5
IS  - 1
SN  - 2051-5960
CY  - London
PB  - Biomed Central
M1  - DZNE-2020-05550
SP  - 31
PY  - 2017
AB  - Frontotemporal Lobar Degeneration (FTLD) encompasses certain related neurodegenerative disorders which alter behaviour, personality and language. Heterogeneous ribonuclear proteins (hnRNPs) maintain RNA metabolism and changes in their function may underpin the pathogenesis of FTLD. Immunostaining for hnRNP A1, A2/B1 and A3 was performed on sections of temporal cortex with hippocampus from 61 patients with FTLD, stratified by pathological hallmarks into FTLD-tau and FTLD-TDP type A, B and C subtypes, and by genetics into patients with C9orf72 expansions, MAPT or GRN mutations, or those without known mutation. Four patients with Motor Neurone Disease (MND) with C9orf72 expansions and 10 healthy controls were also studied. Semi-quantitative analysis assessed hnRNP staining intensity in dentate gyrus (DG) and CA4 region of hippocampus, and temporal cortex (Tcx) in the different pathological and genetic groups.Immunostaining for hnRNP A1, A2/B1 and A3 revealed no consistent changes in pattern or amount of physiological staining across any of the pathological or genetic groups. No immunostaining of any inclusions resembling TDP-43 immunoreactive neuronal cytoplasmic inclusions or dystrophic neurites, was seen in either Tcx or DG of the hippocampus in any of the FTLD cases investigated for hnRNP A1, A2/B1 and A3. However, immunostaining for hnRNP A3 showed that inclusion bodies, resembling those TDP-43 negative, p62-immunopositive structures containing dipeptide repeat proteins (DPR) were variably observed in hippocampus and cerebellum. The proportion of cases showing hnRNP A3-immunoreactive DPR, and the number of hnRNP A3-positive inclusions within cases, was significantly greater in DG than in cells of CA4 region and cerebellum, but the latter was significantly less in all three regions compared to that detected by p62 immunostaining.
KW  - Aged
KW  - Aged, 80 and over
KW  - C9orf72 Protein: genetics
KW  - Cerebellum: metabolism
KW  - Cerebellum: pathology
KW  - DNA Repeat Expansion
KW  - DNA-Binding Proteins: metabolism
KW  - Female
KW  - Frontotemporal Lobar Degeneration: genetics
KW  - Frontotemporal Lobar Degeneration: metabolism
KW  - Frontotemporal Lobar Degeneration: pathology
KW  - Heterogeneous Nuclear Ribonucleoprotein A1: metabolism
KW  - Heterogeneous-Nuclear Ribonucleoprotein Group A-B: metabolism
KW  - Hippocampus: metabolism
KW  - Hippocampus: pathology
KW  - Humans
KW  - Inclusion Bodies: metabolism
KW  - Inclusion Bodies: pathology
KW  - Intercellular Signaling Peptides and Proteins: genetics
KW  - Male
KW  - Middle Aged
KW  - Motor Neuron Disease: genetics
KW  - Motor Neuron Disease: metabolism
KW  - Motor Neuron Disease: pathology
KW  - Progranulins
KW  - Temporal Lobe: metabolism
KW  - Temporal Lobe: pathology
KW  - tau Proteins: genetics
KW  - C9orf72 Protein (NLM Chemicals)
KW  - C9orf72 protein, human (NLM Chemicals)
KW  - DNA-Binding Proteins (NLM Chemicals)
KW  - GRN protein, human (NLM Chemicals)
KW  - HNRNPA3 protein, human (NLM Chemicals)
KW  - Heterogeneous Nuclear Ribonucleoprotein A1 (NLM Chemicals)
KW  - Heterogeneous-Nuclear Ribonucleoprotein Group A-B (NLM Chemicals)
KW  - Intercellular Signaling Peptides and Proteins (NLM Chemicals)
KW  - MAPT protein, human (NLM Chemicals)
KW  - Progranulins (NLM Chemicals)
KW  - TDP-43 protein, human (NLM Chemicals)
KW  - hnRNP A2 (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:28431575
C2  - pmc:PMC5399321
DO  - DOI:10.1186/s40478-017-0437-5
UR  - https://pub.dzne.de/record/139228
ER  -