Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 6 October 2006:
Vol. 314. no. 5796, pp. 130 - 133
DOI: 10.1126/science.1134108
Prev | Table of Contents | Next

Reports

Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis

Manuela Neumann,1,11* Deepak M. Sampathu,1* Linda K. Kwong,1* Adam C. Truax,1 Matthew C. Micsenyi,1 Thomas T. Chou,2 Jennifer Bruce,1 Theresa Schuck,1 Murray Grossman,3,4 Christopher M. Clark,3,4 Leo F. McCluskey,3 Bruce L. Miller,6 Eliezer Masliah,7 Ian R. Mackenzie,8 Howard Feldman,9 Wolfgang Feiden,10 Hans A. Kretzschmar,11 John Q. Trojanowski,1,4,5 Virginia M.-Y. Lee1,4,5{dagger}

Ubiquitin-positive, tau- and {alpha}-synuclein–negative inclusions are hallmarks of frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis. Although the identity of the ubiquitinated protein specific to either disorder was unknown, we showed that TDP-43 is the major disease protein in both disorders. Pathologic TDP-43 was hyper-phosphorylated, ubiquitinated, and cleaved to generate C-terminal fragments and was recovered only from affected central nervous system regions, including hippocampus, neocortex, and spinal cord. TDP-43 represents the common pathologic substrate linking these neurodegenerative disorders.

1 Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
2 Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
3 Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
4 Alzheimer's Disease Core Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
5 Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
6 Department of Neurology, University of California at San Francisco, CA 94117, USA.
7 Department of Neurosciences, University of California San Diego, School of Medicine, La Jolla, CA 92093, USA.
8 Department of Pathology, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada.
9 Division of Neurology, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada.
10 Institute for Neuropathology, University of the Saarland, 66421 Homburg, Germany.
11 Center for Neuropathology and Prion Research, Ludwig-Maximilians University, 81377 Munich, Germany.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: vmylee{at}mail.med.upenn.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Sporadic ALS has compartment-specific aberrant exon splicing and altered cell-matrix adhesion biology.
S. J. Rabin, J. M. H. Kim, M. Baughn, R. T. Libby, Y. J. Kim, Y. Fan, R. T. Libby, A. La Spada, B. Stone, and J. Ravits (2009)
Hum. Mol. Genet.
   Abstract »    Full Text »    PDF »
TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration.
I. Wegorzewska, S. Bell, N. J. Cairns, T. M. Miller, and R. H. Baloh (2009)
PNAS 106, 18809-18814
   Abstract »    Full Text »    PDF »
TARDBP in amyotrophic lateral sclerosis: identification of a novel variant but absence of copy number variation.
D Baumer, N Parkinson, and K Talbot (2009)
J. Neurol. Neurosurg. Psychiatry 80, 1283-1285
   Abstract »    Full Text »    PDF »
A novel TARDBP mutation in an Australian amyotrophic lateral sclerosis kindred.
K L Williams, J C Durnall, A D Thoeng, S T Warraich, G A Nicholson, and I P Blair (2009)
J. Neurol. Neurosurg. Psychiatry 80, 1286-1288
   Abstract »    Full Text »    PDF »
Survival Profiles of Patients With Frontotemporal Dementia and Motor Neuron Disease.
W. T. Hu, H. Seelaar, K. A. Josephs, D. S. Knopman, B. F. Boeve, E. J. Sorenson, L. McCluskey, L. Elman, H. J. Schelhaas, J. E. Parisi, et al. (2009)
Arch Neurol 66, 1359-1364
   Abstract »    Full Text »    PDF »
A new subtype of frontotemporal lobar degeneration with FUS pathology.
M. Neumann, R. Rademakers, S. Roeber, M. Baker, H. A. Kretzschmar, and I. R. A. Mackenzie (2009)
Brain 132, 2922-2931
   Abstract »    Full Text »    PDF »
With or without FUS, it is the anatomy that dictates the dementia phenotype.
S. Weintraub and M. Mesulam (2009)
Brain 132, 2906-2908
   Full Text »    PDF »
Mutations in TDP-43 link glycine-rich domain functions to amyotrophic lateral sclerosis.
G. S. Pesiridis, V. M.-Y. Lee, and J. Q. Trojanowski (2009)
Hum. Mol. Genet. 18, R156-R162
   Abstract »    Full Text »    PDF »
Mutations in FUS cause FALS and SALS in French and French Canadian populations.
V. V. Belzil, P. N. Valdmanis, P. A. Dion, H. Daoud, E. Kabashi, A. Noreau, J. Gauthier, for the S2D team, P. Hince, A. Desjarlais, et al. (2009)
Neurology 73, 1176-1179
   Abstract »    Full Text »    PDF »
Another gene for ALS: Mutations in sporadic cases and the rare variant hypothesis.
K. Talbot (2009)
Neurology 73, 1172-1173
   Full Text »    PDF »
Rapamycin Rescues TDP-43 Mislocalization and the Associated Low Molecular Mass Neurofilament Instability.
A. Caccamo, S. Majumder, J. J. Deng, Y. Bai, F. B. Thornton, and S. Oddo (2009)
J. Biol. Chem. 284, 27416-27424
   Abstract »    Full Text »    PDF »
Reciprocal Efficiency of RNQ1 and Polyglutamine Detoxification in the Cytosol and Nucleus.
P. M. Douglas, D. W. Summers, H.-Y. Ren, and D. M. Cyr (2009)
Mol. Biol. Cell 20, 4162-4173
   Abstract »    Full Text »    PDF »
Truncation and pathogenic mutations facilitate the formation of intracellular aggregates of TDP-43.
T. Nonaka, F. Kametani, T. Arai, H. Akiyama, and M. Hasegawa (2009)
Hum. Mol. Genet. 18, 3353-3364
   Abstract »    Full Text »    PDF »
ALS motor phenotype heterogeneity, focality, and spread: Deconstructing motor neuron degeneration.
J. M. Ravits and A. R. La Spada (2009)
Neurology 73, 805-811
   Abstract »    Full Text »    PDF »
Neurology of anomia in the semantic variant of primary progressive aphasia.
M. Mesulam, E. Rogalski, C. Wieneke, D. Cobia, A. Rademaker, C. Thompson, and S. Weintraub (2009)
Brain 132, 2553-2565
   Abstract »    Full Text »    PDF »
Absence of ubiquitinated inclusions in hypocretin neurons of patients with narcolepsy.
M. Honda, T. Arai, M. Fukazawa, Y. Honda, K. Tsuchiya, A. Salehi, H. Akiyama, and E. Mignot (2009)
Neurology 73, 511-517
   Abstract »    Full Text »    PDF »
TDP-43 Depletion Induces Neuronal Cell Damage through Dysregulation of Rho Family GTPases.
Y. Iguchi, M. Katsuno, J.-i. Niwa, S.-i. Yamada, J. Sone, M. Waza, H. Adachi, F. Tanaka, K.-i. Nagata, N. Arimura, et al. (2009)
J. Biol. Chem. 284, 22059-22066
   Abstract »    Full Text »    PDF »
TDP-43 Is Intrinsically Aggregation-prone, and Amyotrophic Lateral Sclerosis-linked Mutations Accelerate Aggregation and Increase Toxicity.
B. S. Johnson, D. Snead, J. J. Lee, J. M. McCaffery, J. Shorter, and A. D. Gitler (2009)
J. Biol. Chem. 284, 20329-20339
   Abstract »    Full Text »    PDF »
Genetic screen identifies serpin5 as a regulator of the toll pathway and CHMP2B toxicity associated with frontotemporal dementia.
S. T. Ahmad, S. T. Sweeney, J.-A Lee, N. T. Sweeney, and F.-B. Gao (2009)
PNAS 106, 12168-12173
   Abstract »    Full Text »    PDF »
Inhibition of Autophagy Induction Delays Neuronal Cell Loss Caused by Dysfunctional ESCRT-III in Frontotemporal Dementia.
J.-A Lee and F.-B. Gao (2009)
J. Neurosci. 29, 8506-8511
   Abstract »    Full Text »    PDF »
Functional mapping of the interaction between TDP-43 and hnRNP A2 in vivo.
A. D'Ambrogio, E. Buratti, C. Stuani, C. Guarnaccia, M. Romano, Y. M. Ayala, and F. E. Baralle (2009)
Nucleic Acids Res. 37, 4116-4126
   Abstract »    Full Text »    PDF »
Biochemical and genetic evidence for a role of IGHMBP2 in the translational machinery.
M. de Planell-Saguer, D. G. Schroeder, M. C. Rodicio, G. A. Cox, and Z. Mourelatos (2009)
Hum. Mol. Genet. 18, 2115-2126
   Abstract »    Full Text »    PDF »
Chromosome 9p-linked families with frontotemporal dementia associated with motor neuron disease.
I. Le Ber, A. Camuzat, E. Berger, D. Hannequin, A. Laquerriere, V. Golfier, D. Seilhean, G. Viennet, P. Couratier, P. Verpillat, et al. (2009)
Neurology 72, 1669-1676
   Abstract »    Full Text »    PDF »
Aberrant cleavage of TDP-43 enhances aggregation and cellular toxicity.
Y.-J. Zhang, Y.-F. Xu, C. Cook, T. F. Gendron, P. Roettges, C. D. Link, W.-L. Lin, J. Tong, M. Castanedes-Casey, P. Ash, et al. (2009)
PNAS 106, 7607-7612
   Abstract »    Full Text »    PDF »
VCP Mutations Causing Frontotemporal Lobar Degeneration Disrupt Localization of TDP-43 and Induce Cell Death.
M. A. Gitcho, J. Strider, D. Carter, L. Taylor-Reinwald, M. S. Forman, A. M. Goate, and N. J. Cairns (2009)
J. Biol. Chem. 284, 12384-12398
   Abstract »    Full Text »    PDF »
Structural insights into TDP-43 in nucleic-acid binding and domain interactions.
P.-H. Kuo, L. G. Doudeva, Y.-T. Wang, C.-K. J. Shen, and H. S. Yuan (2009)
Nucleic Acids Res. 37, 1799-1808
   Abstract »    Full Text »    PDF »
Frontotemporal dementia presenting as schizophrenia-like psychosis in young people: clinicopathological series and review of cases.
D. Velakoulis, M. Walterfang, R. Mocellin, C. Pantelis, and C. McLean (2009)
The British Journal of Psychiatry 194, 298-305
   Abstract »    Full Text »    PDF »
Expression of TDP-43 C-terminal Fragments in Vitro Recapitulates Pathological Features of TDP-43 Proteinopathies.
L. M. Igaz, L. K. Kwong, A. Chen-Plotkin, M. J. Winton, T. L. Unger, Y. Xu, M. Neumann, J. Q. Trojanowski, and V. M.-Y. Lee (2009)
J. Biol. Chem. 284, 8516-8524
   Abstract »    Full Text »    PDF »
Potentiation of Amyotrophic Lateral Sclerosis (ALS)-associated TDP-43 Aggregation by the Proteasome-targeting Factor, Ubiquilin 1.
S. H. Kim, Y. Shi, K. A. Hanson, L. M. Williams, R. Sakasai, M. J. Bowler, and R. S. Tibbetts (2009)
J. Biol. Chem. 284, 8083-8092
   Abstract »    Full Text »    PDF »
TDP-43 M311V mutation in familial amyotrophic lateral sclerosis.
R Lemmens, V Race, N Hersmus, G Matthijs, L Van Den Bosch, P Van Damme, B Dubois, S Boonen, A Goris, and W Robberecht (2009)
J. Neurol. Neurosurg. Psychiatry 80, 354-355
   Full Text »    PDF »
Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members.
N. Finch, M. Baker, R. Crook, K. Swanson, K. Kuntz, R. Surtees, G. Bisceglio, A. Rovelet-Lecrux, B. Boeve, R. C. Petersen, et al. (2009)
Brain 132, 583-591
   Abstract »    Full Text »    PDF »
Mutations in FUS, an RNA Processing Protein, Cause Familial Amyotrophic Lateral Sclerosis Type 6.
C. Vance, B. Rogelj, T. Hortobagyi, K. J. De Vos, A. L. Nishimura, J. Sreedharan, X. Hu, B. Smith, D. Ruddy, P. Wright, et al. (2009)
Science 323, 1208-1211
   Abstract »    Full Text »    PDF »
Clinical and Pathological Continuum of Multisystem TDP-43 Proteinopathies.
F. Geser, M. Martinez-Lage, J. Robinson, K. Uryu, M. Neumann, N. J. Brandmeir, S. X. Xie, L. K. Kwong, L. Elman, L. McCluskey, et al. (2009)
Arch Neurol 66, 180-189
   Abstract »    Full Text »    PDF »
No TARDBP Mutations in a French Canadian Population of Patients With Parkinson Disease.
E. Kabashi, H. Daoud, J.-B. Riviere, P. N. Valdamanis, P. Bourgouin, P. Provencher, E. Pourcher, P. Dion, N. Dupre, and G. A. Rouleau (2009)
Arch Neurol 66, 281-282
   Full Text »    PDF »
Contribution of TARDBP mutations to sporadic amyotrophic lateral sclerosis.
H Daoud, P N Valdmanis, E Kabashi, P Dion, N Dupre, W Camu, V Meininger, and G A Rouleau (2009)
J. Med. Genet. 46, 112-114
   Abstract »    Full Text »    PDF »
Cause of death and clinical grading criteria in a cohort of amyotrophic lateral sclerosis cases undergoing autopsy from the Scottish Motor Neurone Disease Register.
K M Kurian, R B Forbes, S Colville, and R J Swingler (2009)
J. Neurol. Neurosurg. Psychiatry 80, 84-87
   Abstract »    Full Text »    PDF »
Diffusion Tensor Imaging in Sporadic and Familial (D90A SOD1) Forms of Amyotrophic Lateral Sclerosis.
B. R. Stanton, D. Shinhmar, M. R. Turner, V. C. Williams, S. C. R. Williams, C. R. V. Blain, V. P. Giampietro, M. Catani, P. N. Leigh, P. M. Andersen, et al. (2009)
Arch Neurol 66, 109-115
   Abstract »    Full Text »    PDF »
Amyotrophic Lateral Sclerosis-Plus Syndrome With TAR DNA-Binding Protein-43 Pathology.
L. F. McCluskey, L. B. Elman, M. Martinez-Lage, V. Van Deerlin, W. Yuan, D. Clay, A. Siderowf, and J. Q. Trojanowski (2009)
Arch Neurol 66, 121-124
   Abstract »    Full Text »    PDF »
Longitudinal Cortical Atrophy in Amyotrophic Lateral Sclerosis With Frontotemporal Dementia.
B. Avants, A. Khan, L. McCluskey, L. Elman, and M. Grossman (2009)
Arch Neurol 66, 138-139
   Full Text »    PDF »
Very Early Semantic Dementia With Progressive Temporal Lobe Atrophy: An 8-Year Longitudinal Study.
K. Czarnecki, J. R. Duffy, C. R. Nehl, S. A. Cross, J. R. Molano, C. R. Jack Jr, M. M. Shiung, K. A. Josephs, and B. F. Boeve (2008)
Arch Neurol 65, 1659-1663
   Abstract »    Full Text »    PDF »
Structural determinants of the cellular localization and shuttling of TDP-43.
Y. M. Ayala, P. Zago, A. D'Ambrogio, Y.-F. Xu, L. Petrucelli, E. Buratti, and F. E. Baralle (2008)
J. Cell Sci. 121, 3778-3785
   Abstract »    Full Text »    PDF »
TDP-43 in Cerebrospinal Fluid of Patients With Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis.
P. Steinacker, C. Hendrich, A. D. Sperfeld, S. Jesse, C. A. F. von Arnim, S. Lehnert, A. Pabst, I. Uttner, H. Tumani, V. M.-Y. Lee, et al. (2008)
Arch Neurol 65, 1481-1487
   Abstract »    Full Text »    PDF »
Impaired action knowledge in amyotrophic lateral sclerosis.
M. Grossman, C. Anderson, A. Khan, B. Avants, L. Elman, and L. McCluskey (2008)
Neurology 71, 1396-1401
   Abstract »    Full Text »    PDF »
TDP-43 Overexpression Enhances Exon 7 Inclusion during the Survival of Motor Neuron Pre-mRNA Splicing.
J. K. Bose, I.-F. Wang, L. Hung, W.-Y. Tarn, and C.-K. J. Shen (2008)
J. Biol. Chem. 283, 28852-28859
   Abstract »    Full Text »    PDF »
Distinct genetic forms of frontotemporal dementia.
H. Seelaar, W. Kamphorst, S. M. Rosso, A. Azmani, R. Masdjedi, I. de Koning, J. A. Maat-Kievit, B. Anar, L. D. Kaat, G. J. Breedveld, et al. (2008)
Neurology 71, 1220-1226
   Abstract »    Full Text »    PDF »
Association Between Progranulin and {beta}-Amyloid in Dementia With Lewy Bodies.
G. J. Revuelta, A. Rosso, and C. F. Lippa (2008)
American Journal of Alzheimer's Disease and Other Dementias 23, 488-493
   Abstract »    PDF »
TDP-43 accumulation in inclusion body myopathy muscle suggests a common pathogenic mechanism with frontotemporal dementia.
C C Weihl, P Temiz, S E Miller, G Watts, C Smith, M Forman, P I Hanson, V Kimonis, and A Pestronk (2008)
J. Neurol. Neurosurg. Psychiatry 79, 1186-1189
   Abstract »    Full Text »    PDF »
Two German Kindreds With Familial Amyotrophic Lateral Sclerosis Due to TARDBP Mutations.
P. Kuhnlein, A.-D. Sperfeld, B. Vanmassenhove, V. Van Deerlin, V. M.-Y. Lee, J. Q. Trojanowski, H. A. Kretzschmar, A. C. Ludolph, and M. Neumann (2008)
Arch Neurol 65, 1185-1189
   Abstract »    Full Text »    PDF »
Progranulin genetic variability contributes to amyotrophic lateral sclerosis.
K. Sleegers, N. Brouwers, S. Maurer-Stroh, M. A. van Es, P. V. Damme, P.W.J. van Vught, J. van der Zee, S. Serneels, T. D. Pooter, M. Van den Broeck, et al. (2008)
Neurology 71, 253-259
   Abstract »    Full Text »    PDF »
Enrichment of C-Terminal Fragments in TAR DNA-Binding Protein-43 Cytoplasmic Inclusions in Brain but not in Spinal Cord of Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis.
L. M. Igaz, L. K. Kwong, Y. Xu, A. C. Truax, K. Uryu, M. Neumann, C. M. Clark, L. B. Elman, B. L. Miller, M. Grossman, et al. (2008)
Am. J. Pathol. 173, 182-194
   Abstract »    Full Text »    PDF »
Molecular Pathogenesis of Frontotemporal Lobar Degeneration: Basic Science Seminar in Neurology.
K. Sleegers, S. Kumar-Singh, M. Cruts, and C. Van Broeckhoven (2008)
Arch Neurol 65, 700-704
   Full Text »    PDF »
Longitudinal decline in autopsy-defined frontotemporal lobar degeneration.
M. Grossman, S. X. Xie, D. J. Libon, X. Wang, L. Massimo, P. Moore, L. Vesely, R. Berkowitz, A. Chatterjee, H. B. Coslett, et al. (2008)
Neurology 70, 2036-2045
   Abstract »    Full Text »    PDF »
The ALS/PDC syndrome of Guam and the cycad hypothesis.
J. C. Steele and P. L. McGeer (2008)
Neurology 70, 1984-1990
   Abstract »    Full Text »    PDF »
Variations in the progranulin gene affect global gene expression in frontotemporal lobar degeneration.
A. S. Chen-Plotkin, F. Geser, J. B. Plotkin, C. M. Clark, L. K. Kwong, W. Yuan, M. Grossman, V. M. Van Deerlin, J. Q. Trojanowski, and V. M.-Y. Lee (2008)
Hum. Mol. Genet. 17, 1349-1362
   Abstract »    Full Text »    PDF »
Disturbance of Nuclear and Cytoplasmic TAR DNA-binding Protein (TDP-43) Induces Disease-like Redistribution, Sequestration, and Aggregate Formation.
M. J. Winton, L. M. Igaz, M. M. Wong, L. K. Kwong, J. Q. Trojanowski, and V. M.-Y. Lee (2008)
J. Biol. Chem. 283, 13302-13309
   Abstract »    Full Text »    PDF »
Abnormal TDP-43 immunoreactivity in AD modifies clinicopathologic and radiologic phenotype.
K. A. Josephs, J. L. Whitwell, D. S. Knopman, W. T. Hu, D. A. Stroh, M. Baker, R. Rademakers, B. F. Boeve, J. E. Parisi, G. E. Smith, et al. (2008)
Neurology 70, 1850-1857
   Abstract »    Full Text »    PDF »
Patient Care and Management of Frontotemporal Lobar Degeneration.
L. Massimo and M. Grossman (2008)
American Journal of Alzheimer's Disease and Other Dementias 23, 125-131
   Abstract »    PDF »
Evidence of Multisystem Disorder in Whole-Brain Map of Pathological TDP-43 in Amyotrophic Lateral Sclerosis.
F. Geser, N. J. Brandmeir, L. K. Kwong, M. Martinez-Lage, L. Elman, L. McCluskey, S. X. Xie, V. M.-Y. Lee, and J. Q. Trojanowski (2008)
Arch Neurol 65, 636-641
   Abstract »    Full Text »    PDF »
Atypical frontotemporal lobar degeneration with ubiquitin-positive, TDP-43-negative neuronal inclusions.
I. R. A. Mackenzie, D. Foti, J. Woulfe, and T. A. Hurwitz (2008)
Brain 131, 1282-1293
   Abstract »    Full Text »    PDF »
A yeast TDP-43 proteinopathy model: Exploring the molecular determinants of TDP-43 aggregation and cellular toxicity.
B. S. Johnson, J. M. McCaffery, S. Lindquist, and A. D. Gitler (2008)
PNAS 105, 6439-6444
   Abstract »    Full Text »    PDF »
Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival.
P. Van Damme, A. Van Hoecke, D. Lambrechts, P. Vanacker, E. Bogaert, J. van Swieten, P. Carmeliet, L. Van Den Bosch, and W. Robberecht (2008)
J. Cell Biol. 181, 37-41
   Abstract »    Full Text »    PDF »
Refining Frontotemporal Dementia With Parkinsonism Linked to Chromosome 17: Introducing FTDP-17 (MAPT) and FTDP-17 (PGRN).
B. F. Boeve and M. Hutton (2008)
Arch Neurol 65, 460-464
   Abstract »    Full Text »    PDF »
Diagnosis and management of motor neurone disease.
C. J McDermott and P. J Shaw (2008)
BMJ 336, 658-662
   Full Text »    PDF »
TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis.
J. Sreedharan, I. P. Blair, V. B. Tripathi, X. Hu, C. Vance, B. Rogelj, S. Ackerley, J. C. Durnall, K. L. Williams, E. Buratti, et al. (2008)
Science 319, 1668-1672
   Abstract »    Full Text »    PDF »
TDP-43 regulates retinoblastoma protein phosphorylation through the repression of cyclin-dependent kinase 6 expression.
Y. M. Ayala, T. Misteli, and F. E. Baralle (2008)
PNAS 105, 3785-3789
   Abstract »    Full Text »    PDF »
Frequency and clinical characteristics of progranulin mutation carriers in the Manchester frontotemporal lobar degeneration cohort: comparison with patients with MAPT and no known mutations.
S. M. Pickering-Brown, S. Rollinson, D. Du Plessis, K. E. Morrison, A. Varma, A. M. T. Richardson, D. Neary, J. S. Snowden, and D. M. A. Mann (2008)
Brain 131, 721-731
   Abstract »    Full Text »    PDF »
A distinct clinical, neuropsychological and radiological phenotype is associated with progranulin gene mutations in a large UK series.
J. Beck, J. D. Rohrer, T. Campbell, A. Isaacs, K. E. Morrison, E. F. Goodall, E. K. Warrington, J. Stevens, T. Revesz, J. Holton, et al. (2008)
Brain 131, 706-720
   Abstract »    Full Text »    PDF »
Phenotype variability in progranulin mutation carriers: a clinical, neuropsychological, imaging and genetic study.
I. Le Ber, A. Camuzat, D. Hannequin, F. Pasquier, E. Guedj, A. Rovelet-Lecrux, V. Hahn-Barma, J. van der Zee, F. Clot, S. Bakchine, et al. (2008)
Brain 131, 732-746
   Abstract »    Full Text »    PDF »
Neuron-Specific Expression of Mutant Superoxide Dismutase Is Sufficient to Induce Amyotrophic Lateral Sclerosis in Transgenic Mice.
D. Jaarsma, E. Teuling, E. D. Haasdijk, C. I. De Zeeuw, and C. C. Hoogenraad (2008)
J. Neurosci. 28, 2075-2088
   Abstract »    Full Text »    PDF »
An Aggregate-Inducing Peripherin Isoform Generated through Intron Retention Is Upregulated in Amyotrophic Lateral Sclerosis and Associated with Disease Pathology.
S. Xiao, S. Tjostheim, T. Sanelli, J. R. McLean, P. Horne, Y. Fan, J. Ravits, M. J. Strong, and J. Robertson (2008)
J. Neurosci. 28, 1833-1840
   Abstract »    Full Text »    PDF »
Disrupted Membrane Homeostasis and Accumulation of Ubiquitinated Proteins in a Mouse Model of Infantile Neuroaxonal Dystrophy Caused by PLA2G6 Mutations.
I. Malik, J. Turk, D. J. Mancuso, L. Montier, M. Wohltmann, D. F. Wozniak, R. E. Schmidt, R. W. Gross, and P. T. Kotzbauer (2008)
Am. J. Pathol. 172, 406-416
   Abstract »    Full Text »    PDF »
Missense Mutations in the Progranulin Gene Linked to Frontotemporal Lobar Degeneration with Ubiquitin-immunoreactive Inclusions Reduce Progranulin Production and Secretion.
S. S. Shankaran, A. Capell, A. T. Hruscha, K. Fellerer, M. Neumann, B. Schmid, and C. Haass (2008)
J. Biol. Chem. 283, 1744-1753
   Abstract »    Full Text »    PDF »
Descriptive epidemiology of amyotrophic lateral sclerosis: new evidence and unsolved issues.
G Logroscino, B J Traynor, O Hardiman, A Chio', P Couratier, J D Mitchell, R J Swingler, E Beghi, and for EURALS (2008)
J. Neurol. Neurosurg. Psychiatry 79, 6-11
   Abstract »    Full Text »    PDF »
Distinct MRI Atrophy Patterns in Autopsy-Proven Alzheimer's Disease and Frontotemporal Lobar Degeneration.
G.D. Rabinovici, W.W. Seeley, E.J. Kim, M.L. Gorno-Tempini, K. Rascovsky, T.A. Pagliaro, S.C. Allison, C. Halabi, J.H. Kramer, J.K. Johnson, et al. (2008)
American Journal of Alzheimer's Disease and Other Dementias 22, 474-488
   Abstract »    PDF »
Progressive aphasia secondary to Alzheimer disease vs FTLD pathology.
K. A. Josephs, J. L. Whitwell, J. R. Duffy, W. A. Vanvoorst, E. A. Strand, W. T. Hu, B. F. Boeve, N. R. Graff-Radford, J. E. Parisi, D. S. Knopman, et al. (2008)
Neurology 70, 25-34
   Abstract »    Full Text »    PDF »
A Novel CpG-free Vertebrate Insulator Silences the Testis-specific SP-10 Gene in Somatic Tissues: ROLE FOR TDP-43 IN INSULATOR FUNCTION.
M. M. Abhyankar, C. Urekar, and P. P. Reddi (2007)
J. Biol. Chem. 282, 36143-36154
   Abstract »    Full Text »    PDF »
Frontotemporal Dementia and Mania.
J. D. Woolley, M. R. Wilson, E. Hung, M.-L. Gorno-Tempini, B. L. Miller, and J. Shim (2007)
Am J Psychiatry 164, 1811-1816
   Full Text »    PDF »
Patterns of MRI atrophy in tau positive and ubiquitin positive frontotemporal lobar degeneration.
E J Kim, G D Rabinovici, W W Seeley, C Halabi, H Shu, M W Weiner, S J DeArmond, J Q Trojanowski, M L Gorno-Tempini, B L Miller, et al. (2007)
J. Neurol. Neurosurg. Psychiatry 78, 1375-1378
   Abstract »    Full Text »    PDF »
Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease.
M. Filimonenko, S. Stuffers, C. Raiborg, A. Yamamoto, L. Malerod, E. M.C. Fisher, A. Isaacs, A. Brech, H. Stenmark, and A. Simonsen (2007)
J. Cell Biol. 179, 485-500
   Abstract »    Full Text »    PDF »
Distinct Antemortem Profiles in Patients With Pathologically Defined Frontotemporal Dementia.
M. Grossman, D. J. Libon, M. S. Forman, L. Massimo, E. Wood, P. Moore, C. Anderson, J. Farmer, A. Chatterjee, C. M. Clark, et al. (2007)
Arch Neurol 64, 1601-1609
   Abstract »    Full Text »    PDF »
FRONTOTEMPORAL LOBAR DEGENERATION WITH UPPER MOTOR NEURON DISEASE/ PRIMARY LATERAL SCLEROSIS.
K. A. Josephs and D. W. Dickson (2007)
Neurology 69, 1800-1801
   Full Text »    PDF »
Cognitive impairment in familial ALS.
M. W. Wheaton, A. R. Salamone, D. M. Mosnik, R. O. McDonald, S. H. Appel, H. I. Schmolck, G. M. Ringholz, and P. E. Schulz (2007)
Neurology 69, 1411-1417
   Abstract »    Full Text »    PDF »
TDP-43 Proteinopathy in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis: Protein Misfolding Diseases Without Amyloidosis.
M. Neumann, L. K. Kwong, D. M. Sampathu, J. Q. Trojanowski, and V. M.-Y. Lee (2007)
Arch Neurol 64, 1388-1394
   Abstract »    Full Text »    PDF »
TDP-43 Pathologic Lesions and Clinical Phenotype in Frontotemporal Lobar Degeneration With Ubiquitin-Positive Inclusions.
M. Grossman, E. M. Wood, P. Moore, M. Neumann, L. Kwong, M. S. Forman, C. M. Clark, L. F. McCluskey, B. L. Miller, V. M.-Y. Lee, et al. (2007)
Arch Neurol 64, 1449-1454
   Abstract »    Full Text »    PDF »
Clinicopathologic correlation in PGRN mutations.
S. Davion, N. Johnson, S. Weintraub, M. -M. Mesulam, A. Engberg, M. Mishra, M. Baker, J. Adamson, M. Hutton, R. Rademakers, et al. (2007)
Neurology 69, 1113-1121
   Abstract »    Full Text »    PDF »
Cognition and Amyotrophic Lateral Sclerosis (ALS).
D. Irwin, C. F. Lippa, and J.M. Swearer (2007)
American Journal of Alzheimer's Disease and Other Dementias 22, 300-312
   Abstract »    PDF »
Quantitative Proteomics Identifies Surfactant-Resistant {alpha}-Synuclein in Cerebral Cortex of Parkinsonism-Dementia Complex of Guam but Not Alzheimer's Disease or Progressive Supranuclear Palsy.
W. Yang, R. L. Woltjer, I. Sokal, C. Pan, Y. Wang, M. Brodey, E. R. Peskind, J. B. Leverenz, J. Zhang, D. P. Perl, et al. (2007)
Am. J. Pathol. 171, 993-1002
   Abstract »    Full Text »    PDF »
Dissecting the complexity of frontotemporal dementia: Genotypes, phenotypes, and phenocopies.
C. Klein and V. Bonifati (2007)
Neurology 69, 129-130
   Full Text »    PDF »
Heterogeneity within a large kindred with frontotemporal dementia: A novel progranulin mutation.
A. C. Bruni, P. Momeni, L. Bernardi, C. Tomaino, F. Frangipane, J. Elder, T. Kawarai, C. Sato, S. Pradella, Y. Wakutani, et al. (2007)
Neurology 69, 140-147
   Abstract »    Full Text »    PDF »
TDP-43 in Familial and Sporadic Frontotemporal Lobar Degeneration with Ubiquitin Inclusions.
N. J. Cairns, M. Neumann, E. H. Bigio, I. E. Holm, D. Troost, K. J. Hatanpaa, C. Foong, C. L. White III, J. A. Schneider, H. A. Kretzschmar, et al. (2007)
Am. J. Pathol. 171, 227-240
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)