Abstract
Mutations in the gene progranulin (PGRN) were recently identified as the cause of
some forms of frontotemporal dementia with ubiquitin-positive intraneuronal inclusion
pathology (FTLD-U). The DNA-binding protein, TDP-43, was determined to be a component
of these ubiquitinated inclusions in FTLD-U and amyotrophic lateral sclerosis (ALS)
with dementia (ALS-D). These findings raise many interesting questions as to the shared
pathology and possible common pathologic process between ALS and FTLD-U.
This study examines the immunoexpression of PGRN in ALS patients using immunohistochemical
analysis of post-mortem tissue. Available brain and spinal cord sections of eight
ALS patients, including one case with severe dementia, and eighteen control-aged brains
were stained with anti-PGRN antibodies. We found increased staining for PGRN in motor
tracts with vacuolar degeneration and glial cells in ALS sample spinal cord and brainstem
sections compared to controls. Variable upper motor neuron staining and reactive glia
were seen in ALS motor cortex samples. Frontal lobe and hippocampal sections showed
no consistent differences from control tissues with the exception of the ALS-dementia
case, which showed PGRN immunoexpression in non-motor cortical areas. These results
describe a pattern of increased PGRN expression in areas of active degeneration in
ALS. The meaning of this association is unclear, but may indicate a potential role
for PGRN in the variable expression of motor and cognitive deficits in the ALS–FTD
spectrum.
Keywords
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Article info
Publication history
Accepted:
August 11,
2008
Received in revised form:
July 12,
2008
Received:
July 3,
2007
Identification
Copyright
© 2008 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
