An MND/ALS phenotype associated with C9orf72 repeat expansion: Abundant p62-positive, TDP-43-negative inclusions in cerebral cortex, hippocampus and cerebellum but without associated cognitive decline

Neuropathology

Volumn 32, Issue 5, 2012, Pages 505-514

  Troakes, Claire ^a   Maekawa, Satomi ^a   Wijesekera, Lokesh ^a   Rogelj, Boris ^a   Siklós, László ^c   Bell, Christopher ^a   Smith, Bradley ^a   Newhouse, Stephen ^a   Vance, Caroline ^a   Johnson, Lauren ^a   Hortobágyi, Tibor ^a   Shatunov, Aleksey ^a   Al Chalabi, Ammar ^a   Leigh, Nigel ^a   Shaw, Christopher E ^a   King, Andrew ^a,b   Al Sarraj, Safa ^a,b  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b KING S COLLEGE HOSPITAL   (United Kingdom)

^c INSTITUTE OF BIOCHEMISTRY   (Hungary)

Author keywords

ALS MND; C9orf72; Cerebellum; P62; TDP 43

Indexed keywords

COPPER ZINC SUPEROXIDE DISMUTASE; FUSED IN SARCOMA PROTEIN; REPETITIVE DNA; TAR DNA BINDING PROTEIN;

ADULT; AGED; AMYOTROPHIC LATERAL SCLEROSIS; ARTICLE; BASAL GANGLION; BRAIN CORTEX; BREATHING MUSCLE; CASE REPORT; CELL INCLUSION; CELL LYSATE; CEREBELLUM; CHROMOSOME 9; COGNITIVE DEFECT; CONTROLLED STUDY; DEATH; DEMENTIA; FAMILY HISTORY; FEMALE; GENE MUTATION; GRANULAR CELL; HIPPOCAMPUS; HUMAN; HUMAN TISSUE; IMMUNOREACTIVITY; LIMB WEAKNESS; MALE; MOLECULAR WEIGHT; MOTOR NEURON DISEASE; OPEN READING FRAME; PHENOTYPE; PRIORITY JOURNAL; TDP 43 PROTEINOPATHY; WESTERN BLOTTING;

AGE OF ONSET; AMYOTROPHIC LATERAL SCLEROSIS; BLOTTING, WESTERN; BRAIN; CEREBELLUM; CEREBRAL CORTEX; COGNITION DISORDERS; DNA; DNA-BINDING PROTEINS; FEMALE; FLUORESCENT ANTIBODY TECHNIQUE; HIPPOCAMPUS; HUMANS; IMMUNOHISTOCHEMISTRY; INCLUSION BODIES; MALE; MICROSCOPY, ELECTRON; MIDDLE AGED; MOTOR NEURON DISEASE; PROTEINS; PROTO-ONCOGENE PROTEINS C-MYC; SPINAL CORD; TISSUE BANKS; TRINUCLEOTIDE REPEAT EXPANSION;

EID: 84866600630     PISSN: 09196544     EISSN: 14401789     Source Type: Journal    
DOI: 10.1111/j.1440-1789.2011.01286.x     Document Type: Article

References (40)

1. Neumann M, Sampathu DM, Kwong LK etal. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006; 314: 130-133.
2. Buratti E, Baralle FE. Multiple roles of TDP-43 in gene expression, splicing regulation, and human disease. Front Biosci 2008; 13: 867-878.
3. Tollervey JR, Curk T, Rogelj B etal. Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Nat Neurosci 2011; 14: 452-458.
4. Nishimura AL, Zupunski V, Troakes C etal. Nuclear import impairment causes cytoplasmic trans-activation response DNA-binding protein accumulation and is associated with frontotemporal lobar degeneration. Brain 2010; 133: 1763-1771.
5. Kato S, Shaw P, Wood-Allum C, Leigh N, Shaw C. Neurodegeneration: The Molecular Pathology of Dementia and Movement Disorders. Basel: ISN Neuropath Press, 2003.
6. Rosen DR, Siddique T, Patterson D etal. Mutations in Cu/Zn superoxide-dismutase gene are associated with familial amyotrophic-lateral-sclerosis. Nature 1993; 362: 59-62.
7. Shaw CE, Enayat ZE, Chioza BA etal. Mutations in all five exons of SOD-1 may cause ALS. Ann Neurol 1998; 43: 390-394.
8. Nishimura AL, Mitne-Neto M, Silva HCA etal. A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am J Hum Genet 2004; 75: 822-831.
9. Greenway MJ, Andersen PM, Russ C etal. ANG mutations segregate with familial and "sporadic" amyotrophic lateral sclerosis. Nat Genet 2006; 38: 411-413.
10. Sreedharan J, Blair IP, Tripathi VB etal. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 2008; 319: 1668-1672.
11. Vance C, Rogelj B, Hortobagyi T etal. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 2009; 323: 1208-1211.
12. Maruyama H, Morino H, Ito H etal. Mutations of optineurin in amyotrophic lateral sclerosis. Nature 2010; 465: 223-226.
13. Hortobagyi T, Troakes C, Nishimura AL etal. Optineurin inclusions occur in a minority of TDP-43 positive ALS and FTLD-TDP cases and are rarely observed in other neurodegenerative disorders. Acta Neuropathol (Berl) 2011; 121: 519-527.
14. Vance C, Al-Chalabi A, Ruddy D etal. Familial amyotrophic lateral sclerosis with frontotemporal dementia is linked to a locus on chromosome 9p13.2-21.3. Brain 2006; 129: 868-876.
15. Pearson JP, Williams NM, Majounie E etal. Familial frontotemporal dementia with amyotrophic lateral sclerosis and a shared haplotype on chromosome 9p. J Neurol 2011; 258: 647-655.
16. Shatunov A, Mok K, Newhouse S etal. Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries: a genome-wide association study. Lancet Neurol 2010; 10: 986-994.
17. Renton AE, Majounie E, Waite A etal. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-Linked ALS-FTD. Neuron 2011; 72: 257-268.
18. Dejesus-Hernandez M, Mackenzie IR, Boeve BF etal. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-Linked FTD and ALS. Neuron 2011; 72: 245-256.
19. Hirano A, Kurland LT, Sayre GP. Familial amyotrophic lateral sclerosis. A subgroup characterized by posterior and spinocerebellar tract involvement and hyaline inclusions in the anterior horn cells. Arch Neurol 1967; 16: 232-243.
20. Maekawa S, Leigh PN, King A etal. TDP-43 is consistently co-localized with ubiquitinated inclusions in sporadic and Guam amyotrophic lateral sclerosis but not in familial amyotrophic lateral sclerosis with and without SOD1 mutations. Neuropathology 2009; 29: 672-683.
21. Cairns NJ, Neumann M, Bigio EH etal. TDP-43 in familial and sporadic frontotemporal lobar degeneration with ubiquitin inclusions. Am J Pathol 2007; 171: 227-240.
22. Mackenzie IRA, Neumann M, Bigio EH etal. Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: an update. Acta Neuropathol (Berl) 2010; 119: 1-4.
23. Mackenzie IR, Neumann M, Bigio EH etal. Nomenclature for neuropathologic subtypes of frontotemporal lobar degeneration: consensus recommendations. Acta Neuropathol (Berl) 2009; 117: 15-18.
24. Pikkarainen M, Hartikainen P, Alafuzoff I. Neuropathologic features of frontotemporal lobar degeneration with ubiquitin-positive inclusions visualized with ubiquitin-binding protein p62 immunohistochemistry. J Neuropathol Exp Neurol 2008; 67: 280-298.
25. King A, Maekawa S, Bodi I, Troakes C, Al-Sarraj S. Ubiquitinated, p62 immunopositive cerebellar cortical neuronal inclusions are evident across the spectrum of TDP-43 proteinopathies but are only rarely additionally immunopositive for phosphorylation-dependent TDP-43. Neuropathology 2011; 31: 239-249.
26. Alafuzoff I, Arzberger T, Al-Sarraj S etal. Staging of neurofibrillary pathology in Alzheimer's disease: a study of the BrainNet Europe Consortium. Brain Pathol 2008; 18: 484-496.
27. Maxwell MH. Two rapid and simple methods used for the removal of resins from 1.0 micron thick epoxy sections. J Microsc 1978; 112: 253-255.
28. Richardson KC, Jarett L, Finke EH. Embedding in epoxy resins for ultrathin sectioning in electron microscopy. Stain Technol 1960; 35: 313-323.
29. Pease DC. Histological Techniques for Electron Microscopy. New York: Academic press, 1960.
30. Reynolds ES. The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol 1963; 17: 208-212.
31. Cairns NJ, Bigio EH, Mackenzie IR etal. Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol (Berl) 2007; 114: 5-22.
32. Boxer AL, Mackenzie IR, Boeve BF etal. Clinical, neuroimaging and neuropathological features of a new chromosome 9p-linked FTD-ALS family. J Neurol Neurosurg Psychiatry 2011; 82: 196-203.
33. Al Sarraj S, King A, Troakes C etal. p62 positive, TDP-43 negative, neuronal cytoplasmic and intranuclear inclusions in the cerebellum and hippocampus define the pathology of C9orf72 linked FTLD and MND/ALS. Acta Neuropathol (Berl) 2011; 122: 691-702.
34. Zatloukal K, Stumptner C, Fuchsbichler A etal. p62 is a common component of cytoplasmic inclusions in protein aggregation diseases. Am J Pathol 2002; 160: 255-263.
35. Pankiv S, Clausen TH, Lamark T etal. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 2007; 282: 24131-24145.
36. Van Deerlin VM, Leverenz JB, Bekris LM etal. TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis. Lancet Neurol 2008; 7: 409-416.
37. Yokoseki A, Shiga A, Tan CF etal. TDP-43 mutation in familial amyotrophic lateral sclerosis. Ann Neurol 2008; 63: 538-542.
38. Baker M, Mackenzie IR, Pickering-Brown SM etal. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 2006; 442: 916-919.
39. Seilhean D, Cazeneuve C, Thuries V etal. Accumulation of TDP-43 and alpha-actin in an amyotrophic lateral sclerosis patient with the K17I ANG mutation. Acta Neuropathol (Berl) 2009; 118: 561-573.
40. Todd PK, Paulson HL. RNA-mediated neurodegeneration in repeat expansion disorders. Ann Neurol 2010; 67: 291-300.