Microglial upregulation of progranulin as a marker of motor neuron degeneration

Thomas Philips, Louis De Muynck, Hoai Nguyen Thi Thu, Bea Weynants, Peter Vanacker, Joke Dhondt, Kristel Sleegers, Helenius J. Schelhaas, Marcel Verbeek, Rik Vandenberghe, Raf Sciot, Christine Van Broeckhoven, Diether Lambrechts, Fred Van Leuven, Ludo Van Den Bosch, Wim Robberecht, Philip Van Damme

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1191-1200
Number of pages10
JournalJournal of neuropathology and experimental neurology
Issue number12
StatePublished - Dec 2010
Externally publishedYes


  • Amyotrophic lateral sclerosis
  • Frontotemporal lobar degeneration
  • Microglia
  • Progranulin
  • Tau

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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