The muscle protein dysferlin accumulates in the Alzheimer brain

James E. Galvin, Divya Palamand, Jeff Strider, Margherita Milone, Alan Pestronk

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 Aβ 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 Aβ deposits accumulating in the AD brain.

Original languageEnglish (US)
Pages (from-to)665-671
Number of pages7
JournalActa Neuropathologica
Volume112
Issue number6
DOIs
StatePublished - Dec 2006

Fingerprint

Muscle Proteins
Alzheimer Disease
Brain
formic acid
Salts
Octoxynol
Neurites
Proteins
Muscles
Serial Extraction
Pyramidal Cells
Amyloid Plaques
Muscular Diseases
Solubility
Dementia
Buffers
Extremities
Western Blotting
Neurons
Mutation

Keywords

  • Alzheimer's disease
  • Amyloid β-protein
  • Dysferlin
  • Neurodegeneration
  • Protein aggregation
  • Tau protein

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

The muscle protein dysferlin accumulates in the Alzheimer brain. / Galvin, James E.; Palamand, Divya; Strider, Jeff; Milone, Margherita; Pestronk, Alan.

In: Acta Neuropathologica, Vol. 112, No. 6, 12.2006, p. 665-671.

Research output: Contribution to journalArticle

Galvin, JE, Palamand, D, Strider, J, Milone, M & Pestronk, A 2006, 'The muscle protein dysferlin accumulates in the Alzheimer brain', Acta Neuropathologica, vol. 112, no. 6, pp. 665-671. https://doi.org/10.1007/s00401-006-0147-8
Galvin, James E. ; Palamand, Divya ; Strider, Jeff ; Milone, Margherita ; Pestronk, Alan. / The muscle protein dysferlin accumulates in the Alzheimer brain. In: Acta Neuropathologica. 2006 ; Vol. 112, No. 6. pp. 665-671.
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