CoChat
Sign Up
Cited by 36Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

The muscle protein dysferlin accumulates in the Alzheimer brain

Open access
Galvin, James E., Palamand, Divya, Strider, Jeff, Milone, Margherita, Pestronk, Alan·2006·Acta Neuropathologica
DOI 10.1007/s00401-006-0147-8PMC PMC1705477
Open this paper in CoChat — free accountOpen PDF

Abstract

Dysferlin is a transmembrane protein that is highly expressed in muscle. Dysferlin mutations cause limb-girdle dystrophy type 2B, Miyoshi myopathy and distal anterior compartment myopathy. Dysferlin has also been described in neural tissue. We studied dysferlin distribution in the brains of patients with Alzheimer disease (AD) and controls. Twelve brains, staged using the Clinical Dementia Rating were examined: 9 AD cases (mean age: 85.9 years and mean disease duration: 8.9 years), and 3 age-matched controls (mean age: 87.5 years). Dysferlin is a cytoplasmic protein in the pyramidal neurons of normal and AD brains. In addition, there were dysferlin-positive dystrophic neurites within A beta plaques in the AD brain, distinct from tau-positive neurites. Western blots of total brain protein (RIPA) and sequential extraction buffers (high salt, high salt/Triton X-100, SDS and formic acid) of increasing protein extraction strength were performed to examine solubility state. In RIPA fractions, dysferlin was seen as 230-272 kDa bands in normal and AD brains. In serial extractions, there was a shift of dysferlin from soluble phase in high salt/Triton X-100 to the more insoluble SDS fraction in AD. Dysferlin is a new protein described in the AD brain that accumulates in association with neuritic plaques. In muscle, dysferlin plays a role in the repair of muscle membrane damage. The accumulation of dysferlin in the AD brain may be related to the inability of neurons to repair damage due to A beta deposits accumulating in the AD brain.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1007/s00401-006-0147-8

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 30

  1. [1]Aoki M Liu J Richard I Bashir R Britton S Keers SM Oeltjen J Brown HE Marchand S Bourg N Beley C McKenna-Yasek D Arahata K Bohlega S Cupler E Illa I Majneh I Barohn RJ Urtizberea JA Fardeau M Amato A Angelini C Bushby K Beckmann JS Brown RH Genomic organization of the dysferlin gene and novel mutations in Miyoshi myopathy Neurology 2001 57 271 278 10.1159/000047245 11468312 Aoki M, Liu J, Richard I, Bashir R, Britton S, Keers SM, Oeltjen J, Brown HE, Marchand S, Bourg N, Beley C, McKenna-Yasek D, Arahata K, Bohlega S, Cupler E, Illa I, Majneh I, Barohn RJ, Urtizberea JA, Fardeau M, Amato A, Angelini C, Bushby K, Beckmann JS, Brown RH Jr (2001) Genomic organization of the dysferlin gene and novel mutations in Miyoshi myopathy. Neurology 57:271–278 11468312 · DOI
  2. [2]Askanas V Engel WK Proposed pathogenetic cascade of inclusion-body myositis: importance of amyloid-beta, misfolded proteins, predisposing genes, and aging Curr Opin Rheumatol 2003 15 737 744 10.1097/00002281-200311000-00009 14569203 Askanas V, Engel WK (2003) Proposed pathogenetic cascade of inclusion-body myositis: importance of amyloid-beta, misfolded proteins, predisposing genes, and aging. Curr Opin Rheumatol 15:737–744 14569203 · DOI
  3. [3]Bansal D Campbell KP Dysferlin and the plasma membrane repair in muscular dystrophy Trends Cell Biol 2004 14 4 206 13 10.1016/j.tcb.2004.03.001 15066638 Bansal D, Campbell KP (2004) Dysferlin and the plasma membrane repair in muscular dystrophy. Trends Cell Biol 14(4):206–13 15066638 · DOI
  4. [5]Bashir R Britton S Strachan T Keers S Vafiadaki E Lako M Richard I Marchand S Bourg N Argov Z Sadeh M Mahjneh I Marconi G Passos-Bueno MR Moreira Ede S Zatz M Beckmann JS Bushby K A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B Nat Genet 1998 20 37 42 10.1038/1689 9731527 Bashir R, Britton S, Strachan T, Keers S, Vafiadaki E, Lako M, Richard I, Marchand S, Bourg N, Argov Z, Sadeh M, Mahjneh I, Marconi G, Passos-Bueno MR, Moreira Ede S, Zatz M, Beckmann JS, Bushby K (1998) A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B. Nat Genet 20:37–42 9731527 · DOI
  5. [6]Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K (2006) Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol, PMID: 16906426 PMC3906709 16906426
  6. [7]Britton S Freeman T Vafiadaki E Keers S Harrison R Bushby K Bashir R The third human FER-1-like protein is highly similar to dysferlin Genomics 2000 68 313 321 10.1006/geno.2000.6290 10995573 Britton S, Freeman T, Vafiadaki E, Keers S, Harrison R, Bushby K, Bashir R (2000) The third human FER-1-like protein is highly similar to dysferlin. Genomics 68:313–321 10995573 · DOI
  7. [8]Caughey B Lansbury PT Proto fibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders Annu Rev Neurosci 2003 26 267 298 10.1146/annurev.neuro.26.010302.081142 12704221 Caughey B, Lansbury PT Jr (2003) Proto fibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders. Annu Rev Neurosci 26:267–298 12704221 · DOI · Paper page
  8. [9]Cenacchi G Fanin M Giorgi LB Angelini C Ultrastructural changes in dysferlinopathy support defective membrane repair mechanism J Clin Pathol 2005 58 190 195 10.1136/jcp.2004.018978 PMC1770568 15677541 Cenacchi G, Fanin M, De Giorgi LB, Angelini C (2005) Ultrastructural changes in dysferlinopathy support defective membrane repair mechanism. J Clin Pathol 58:190–195 15677541 PMC1770568 · DOI
  9. [10]Davis DB Delmonte AJ Ly CT McNally EM Myoferlin, a candidate gene and potential modifier of muscular dystrophy Hum Mol Genet 2000 9 217 226 10.1093/hmg/9.2.217 10607832 Davis DB, Delmonte AJ, Ly CT, McNally EM (2000) Myoferlin, a candidate gene and potential modifier of muscular dystrophy. Hum Mol Genet 9:217–226 10607832 · DOI
  10. [11]Dermaut B Kumar-Singh S Rademakers R Theuns J Cruts M Broeckhoven C Tau is central in the genetic Alzheimer-frontotemporal dementia spectrum Trends Genet 2005 21 664 672 10.1016/j.tig.2005.09.005 16221505 Dermaut B, Kumar-Singh S, Rademakers R, Theuns J, Cruts M, Van Broeckhoven C (2005) Tau is central in the genetic Alzheimer-frontotemporal dementia spectrum. Trends Genet 21:664–672 16221505 · DOI
  11. [12]Doherty KR McNally EM Repairing the tears: dysferlin in muscle membrane repair Trends Mol Med 2003 9 327 330 10.1016/S1471-4914(03)00136-9 12928033 Doherty KR, McNally EM (2003) Repairing the tears: dysferlin in muscle membrane repair. Trends Mol Med 9:327–330 12928033 · DOI
  12. [13]Galvin JE Lee VM-Y Trojanowski JQ Synucleinopathies: Clinical and pathological implications Arch Neurol 2000 58 186 190 10.1001/archneur.58.2.186 11176955 Galvin JE, Lee VM-Y, Trojanowski JQ (2000) Synucleinopathies: Clinical and pathological implications. Arch Neurol 58:186–190 11176955 · DOI
  13. [14]Galvin JE Powlishta KK Wilkins K McKeel DW Storandt M Grant E Morris JC Predictors of preclinical Alzheimer disease and dementia: a clinicopathologic study Arch Neurol 2005 62 758 765 10.1001/archneur.62.5.758 15883263 Galvin JE, Powlishta KK, Wilkins K, McKeel Jr DW, Storandt M, Grant E, Morris JC (2005) Predictors of preclinical Alzheimer disease and dementia: a clinicopathologic study. Arch Neurol 62:758–765 15883263 · DOI · Paper page
  14. [15]Galvin JE Detection of aggregates and protein inclusions by staining of tissues Methods Mol Biol 2003 232 149 164 12840547 Galvin JE (2003) Detection of aggregates and protein inclusions by staining of tissues. Methods Mol Biol 232:149–164 12840547
  15. [16]Galvin JE Giasson BI Hurtig HI Lee VMY Trojanowski JQ Neurodegeneration with brain iron accumulation, type 1 (NBIA 1) is characterized by α-, β-, and γ-synuclein neuropathology Am J Pathol 2000 157 361 368 PMC1850114 10934140 Galvin JE, Giasson BI, Hurtig HI, Lee VMY, Trojanowski JQ (2000) Neurodegeneration with brain iron accumulation, type 1 (NBIA 1) is characterized by α-, β-, and γ-synuclein neuropathology. Am J Pathol 157:361–368 10934140 PMC1850114
  16. [17]Galvin JE Gene expression profiling the neuropathology of neurodegenerative disease Neurochem Res 2004 29 1041 1051 10.1023/B:NERE.0000023592.53769.4d 15176462 Galvin JE (2004) Gene expression profiling the neuropathology of neurodegenerative disease. Neurochem Res 29:1041–1051 15176462 · DOI
  17. [18]Goedert M Filamentous nerve cell inclusions in neurodegenerative diseases: tauopathies and alpha-synucleinopathies Philos Trans R Soc Lond B Biol Sci 1999 354 1101 1118 10.1098/rstb.1999.0466 PMC1692614 10434313 Goedert M (1999) Filamentous nerve cell inclusions in neurodegenerative diseases: tauopathies and alpha-synucleinopathies. Philos Trans R Soc Lond B Biol Sci 354:1101–1118 10434313 PMC1692614 · DOI
  18. [19]Hayashi YK Membrane-repair machinery and muscular dystrophy Lancet 2003 362 843 844 10.1016/S0140-6736(03)14346-2 13678966 Hayashi YK (2003) Membrane-repair machinery and muscular dystrophy. Lancet 362:843–844 13678966 · DOI
  19. [20]Ho M Gallardo E McKenna-Yasek D Luna N Illa I Brown RH A novel, blood-based diagnostic assay for limb girdle muscular dystrophy 2B and Miyoshi myopathy Ann Neurol 2002 51 129 133 10.1002/ana.10080 11782994 Ho M, Gallardo E, McKenna-Yasek D, De Luna N, Illa I, Brown Jr RH (2002) A novel, blood-based diagnostic assay for limb girdle muscular dystrophy 2B and Miyoshi myopathy. Ann Neurol 51:129–133 11782994 · DOI
  20. [21]Ho M Post CM Donahue LR Lidov HG Bronson RT Goolsby H Watkins SC Cox GA Brown RH Disruption of muscle membrane and phenotype divergence in two novel mouse models of dysferlin deficiency Hum Mol Genet 2004 13 1999 2010 10.1093/hmg/ddh212 15254015 Ho M, Post CM, Donahue LR, Lidov HG, Bronson RT, Goolsby H, Watkins SC, Cox GA, Brown RH Jr (2004) Disruption of muscle membrane and phenotype divergence in two novel mouse models of dysferlin deficiency. Hum Mol Genet 13:1999–2010 15254015 · DOI · Paper page
  21. [22]Hoffman EP Brown RH Kunkel LM Dystrophin: the protein product of the Duchenne muscular dystrophy locus Cell 1987 51 919 928 10.1016/0092-8674(87)90579-4 3319190 Hoffman EP, Brown RH Jr, Kunkel LM (1987) Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51:919–928 3319190 · DOI · Paper page
  22. [23]Holzfeind PJ Grewal PK Reitsamer HA Kechvar J Lassmann H Hoeger H Hewitt JE Bittner RE Skeletal, cardiac and tongue muscle pathology, defective retinal transmission, and neuronal migration defects in the Large(myd) mouse defines a natural model for glycosylation-deficient muscle–eye–brain disorders Hum Mol Genet 2002 11 2673 2687 10.1093/hmg/11.21.2673 12354792 Holzfeind PJ, Grewal PK, Reitsamer HA, Kechvar J, Lassmann H, Hoeger H, Hewitt JE, Bittner RE (2002) Skeletal, cardiac and tongue muscle pathology, defective retinal transmission, and neuronal migration defects in the Large(myd) mouse defines a natural model for glycosylation-deficient muscle–eye–brain disorders. Hum Mol Genet 11:2673–2687 12354792 · DOI
  23. [24]Illa I Serrano-Munuera C Gallardo E Lasa A Rojas-Garcia R Palmer J Gallano P Baiget M Matsuda C Brown RH Distal anterior compartment myopathy: a dysferlin mutation causing a new muscular dystrophy phenotype Ann Neurol 2001 49 130 134 10.1002/1531-8249(200101)49:1<130::AID-ANA22>3.0.CO;2-0 11198284 Illa I, Serrano-Munuera C, Gallardo E, Lasa A, Rojas-Garcia R, Palmer J, Gallano P, Baiget M, Matsuda C, Brown RH (2001) Distal anterior compartment myopathy: a dysferlin mutation causing a new muscular dystrophy phenotype. Ann Neurol 49:130–134 11198284 · DOI
  24. [26]McKhann G Drachman D Folstein M Katzman R Price D Stadlan EM Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease Neurology 1984 34 939 944 6610841 McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology 34:939–944 6610841
  25. [27]Morris JC The Clinical Dementia Rating (CDR): current version and scoring rules Neurology 1993 43 2412 2414 8232972 Morris JC (1993) The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 43:2412–2414 8232972
  26. [28]National Institute on Aging, Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer’s Disease (1997) Consensus recommendations for the postmortem diagnosis of Alzheimer’s disease. Neurobiol Aging 18(S4):S1–S2 9330978
  27. [29]Salani S Lucchiari S Fortunato F Crimi M Corti S Locatelli F Bossolasco P Bresolin N Comi GP Developmental and tissue-specific regulation of a novel dysferlin isoform Muscle Nerve 2004 30 366 374 10.1002/mus.20106 15318348 Salani S, Lucchiari S, Fortunato F, Crimi M, Corti S, Locatelli F, Bossolasco P, Bresolin N, Comi GP (2004) Developmental and tissue-specific regulation of a novel dysferlin isoform. Muscle Nerve 30:366–374 15318348 · DOI
  28. [30]Sharma MC Goebel HH Protein aggregate myopathies Neurol India 2005 53 273 279 16230791 Sharma MC, Goebel HH (2005) Protein aggregate myopathies. Neurol India 53:273–279 16230791
  29. [31]Spillantini MG Tolnay M Love S Goedert M Microtubule-associated protein tau, heparan sulphate, and α-synuclein in several neurodegenerative diseases with dementia Acta Neuropathol 1999 97 585 594 10.1007/s004010051034 10378377 Spillantini MG, Tolnay M, Love S, Goedert M (1999) Microtubule-associated protein tau, heparan sulphate, and α-synuclein in several neurodegenerative diseases with dementia. Acta Neuropathol 97:585–594 10378377 · DOI
  30. [32]Yasunaga S Grati M Cohen-Salmon M El-Amraoui A Mustapha M Salem N El-Zir E Loiselet J Petit C A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness Nat Genet 1999 21 363 369 10.1038/7693 10192385 Yasunaga S, Grati M, Cohen-Salmon M, El-Amraoui A, Mustapha M, Salem N, El-Zir E, Loiselet J, Petit C (1999) A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness. Nat Genet 21:363–369 10192385 · DOI

Cited by

Sorted by citations

Authors
Galvin, J. E., Palamand, D., Strider, J., Milone, M., & Pestronk, A.
Affiliations
Washington University in St. Louis (US)
Corresponding author
Galvin, James E.
ORCID
Venue
Acta Neuropathologica
Publisher
Springer Science and Business Media LLC
Published
2006-10-06
Volume
112
Issue
6
Pages
665-71
ISSN
  • 0001-6322 (ISSN-L)
  • 1432-0533
DOI
10.1007/s00401-006-0147-8
PMC
PMC1705477
OpenAlex
W1984643176
Cited by
36
References
2
Citations by year
2025: 5 · 2024: 3 · 2023: 5 · 2022: 1 · 2021: 2 · 2020: 1 · 2018: 3 · 2017: 1 · 2015: 1 · 2014: 2 · 2013: 2
FWCI
1.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Neuropathologica (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Federation for Aging Research
  • National Institute on Aging (AG03991, K08 AG20764, AG 05681, K08AG020764, P01 AG05681, P50AG005681, P01AG003991, AG20764, P50 AG03991)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
dysferlin, Alzheimer's disease, amyloid plaques, neuritic plaques, dystrophic neurites, protein solubility, pyramidal neurons, Miyoshi myopathy
MeSH terms
Dysferlin, Aged, 80 and over, Alzheimer Disease, Brain, Female, Humans, Immunohistochemistry, Male, Membrane Proteins, Muscle Proteins, Blotting, Western, Plaque, Amyloid

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review