title: Telomere shortening leads to earlier age of onset in ALS mice.
abstract: Telomere shortening has been linked to a variety of neurodegenerative diseases. Recent evidence suggests that reduced telomerase expression results in shorter telomeres in leukocytes from sporadic patients with amyotrophic lateral sclerosis (ALS) compared with healthy controls. Here, we have characterized telomere length in microglia, astroglia and neurons in human post mortem brain tissue from ALS patients and healthy controls. Moreover, we studied the consequences of telomerase deletion in a genetic mouse model for ALS. We found a trend towards longer telomeres in microglia in the brains of ALS patients compared to non-neurologic controls. Knockout of telomerase leading to telomere shortening accelerated the ALS phenotype inSOD1G93A-transgenic mice. Our results suggest that telomerase dysfunction might contribute to the age-related risk for ALS.
authors.affiliation: Department of Neurology, Ulm University, 89081 Ulm, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Linkus
authors.affiliation: Department of Neurology, Ulm University, 89081 Ulm, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Wiesner
authors.affiliation: Department of Neurology, Ulm University, 89081 Ulm, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Meßner
authors.affiliation: Department of Clinical and Biological Psychology, Ulm University, 89081 Ulm, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Karabatsiakis
authors.affiliation: Department of Internal Medicine III, Ulm University, 89081 Ulm, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Scheffold
authors.affiliation: Leibniz Institute for Age Research, 07745 Jena, Germany.
authors.forename: K Lenhard
authors.initials: KL
authors.lastname: Rudolph
authors.affiliation: Department of Pathology, Ulm University, 89081 Ulm, Germany.|Current address: KU Leuven, Department of Neuroscience, B-3000 Leuven, Belgium.
authors.forename: Dietmar R
authors.initials: DR
authors.lastname: Thal
authors.affiliation: Department of Neurology, Ulm University, 89081 Ulm, Germany.
authors.forename: Jochen H
authors.initials: JH
authors.lastname: Weishaupt
authors.affiliation: Department of Neurology, Ulm University, 89081 Ulm, Germany.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Ludolph
authors.affiliation: Department of Neurology, Ulm University, 89081 Ulm, Germany.
authors.forename: Karin M
authors.initials: KM
authors.lastname: Danzer
mesh_terms: D017668:Age of Onset; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D000818:Animals; D001253:Astrocytes / Q000473:pathology; D001921:Brain / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017628:Microglia / Q000473:pathology; D009474:Neurons / Q000473:pathology; D016615:Telomere / Q000473:pathology*; D059506:Telomere Shortening / Q000502:physiology*
keywords: amyotrophic lateral sclerosis; astroglia; microglia; telomerase dysfunction; telomere length