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.