TY - JOUR
T1 - Microglial upregulation of progranulin as a marker of motor neuron degeneration
AU - Philips, Thomas
AU - De Muynck, Louis
AU - Thu, Hoai Nguyen Thi
AU - Weynants, Bea
AU - Vanacker, Peter
AU - Dhondt, Joke
AU - Sleegers, Kristel
AU - Schelhaas, Helenius J.
AU - Verbeek, Marcel
AU - Vandenberghe, Rik
AU - Sciot, Raf
AU - Van Broeckhoven, Christine
AU - Lambrechts, Diether
AU - Van Leuven, Fred
AU - Van Den Bosch, Ludo
AU - Robberecht, Wim
AU - Van Damme, Philip
PY - 2010/12
Y1 - 2010/12
N2 - Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are overlapping neurodegenerative disorders. Mutations in the growth factor progranulin (PGRN) gene cause FTLD, sometimes in conjunction with ALS; such mutations are also observed in some ALS patients. Most PGRN mutations underlying FTLD are null mutations that result in reduced PGRN levels. We investigated PGRN expression in human ALS and in mouse models of motor neuron degeneration. Progranulin plasma or CSF levels in newly diagnosed ALS patients did not differ from those in healthy or disease controls (PGRN mutation-negative FTLD and Alzheimer disease patients). In the mutant SOD1G93 Amouse model of ALS, spinal cord PGRN levels were normal in presymptomatic animals but increased during the degenerative process. This increase in PGRN correlated with enhanced expression of PGRN in microglia. In CSF, PGRN levels were normal in presymptomatic and early symptomatic animals, but with disease progression, a raise in PGRN was detectable. These data indicate that upregulation of PGRN is a marker of the microglial response that occurs with progression in motor neuron diseases.
AB - Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are overlapping neurodegenerative disorders. Mutations in the growth factor progranulin (PGRN) gene cause FTLD, sometimes in conjunction with ALS; such mutations are also observed in some ALS patients. Most PGRN mutations underlying FTLD are null mutations that result in reduced PGRN levels. We investigated PGRN expression in human ALS and in mouse models of motor neuron degeneration. Progranulin plasma or CSF levels in newly diagnosed ALS patients did not differ from those in healthy or disease controls (PGRN mutation-negative FTLD and Alzheimer disease patients). In the mutant SOD1G93 Amouse model of ALS, spinal cord PGRN levels were normal in presymptomatic animals but increased during the degenerative process. This increase in PGRN correlated with enhanced expression of PGRN in microglia. In CSF, PGRN levels were normal in presymptomatic and early symptomatic animals, but with disease progression, a raise in PGRN was detectable. These data indicate that upregulation of PGRN is a marker of the microglial response that occurs with progression in motor neuron diseases.
KW - Amyotrophic lateral sclerosis
KW - Frontotemporal lobar degeneration
KW - Microglia
KW - Progranulin
KW - Tau
UR - http://www.scopus.com/inward/record.url?scp=78650178041&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650178041&partnerID=8YFLogxK
U2 - 10.1097/NEN.0b013e3181fc9aea
DO - 10.1097/NEN.0b013e3181fc9aea
M3 - Article
C2 - 21107132
AN - SCOPUS:78650178041
VL - 69
SP - 1191
EP - 1200
JO - Journal of Neuropathology and Experimental Neurology
JF - Journal of Neuropathology and Experimental Neurology
SN - 0022-3069
IS - 12
ER -