Journal
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
Volume 69, Issue 12, Pages 1191-1200Publisher
OXFORD UNIV PRESS INC
DOI: 10.1097/NEN.0b013e3181fc9aea
Keywords
Amyotrophic lateral sclerosis; Frontotemporal lobar degeneration; Microglia; Progranulin; Tau
Categories
Funding
- Fund for Scientific Research Flanders [FWO-V 1.5.081.08]
- Belgian Federal Science Policy Office [P6/43]
- FWO-V
- Stichting voor Alzheimer Onderzoek-Belgium (SAO-FRMA) [08615]
- Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen)
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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 SOD1(G93A) mouse 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.
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