|ITEM METADATA RECORD
|Title: ||Tau doesn't contribute to the pathogenesis of amyotrophic lateral sclerosis|
|Authors: ||Taes, Ines|
Van Es, M
van den Berg, L
Van Den Bosch, Ludo
Van Damme, Philip
Robberecht, Wim #
|Issue Date: ||2008 |
|Publisher: ||The Society for Neuroscience|
|Host Document: ||Journal of Neuroscience vol:online program planner|
|Conference: ||Neuroscience location:Washington date:15-19 November 2008|
|Abstract: ||Neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) are characterized by axonal dysfunction. Microtubules and their associated proteins, as well as neurofilaments, are the main components of axonal architecture, and have been hypothesized to contribute to the pathogenic mechanism of motor neuron degeneration in ALS. Aberrant phosphorylation of the microtubule-associated protein tau has been found in brain tissue of ALS patients and in the spinal cord of the mutant SOD1 mouse, a rodent model for ALS. In addition, a possible but not conclusive genetic association between polymorphisms in the tau-encoding MAPT gene and the occurrence of ALS has been reported.
In the present study, we investigated the possible association of the H1/H2 polymorphism in MAPT in 2676 well-characterized ALS patients and 7973 controls from seven cohorts. Despite the well-powered study population, no association was observed in a combined analysis (H1/H1: OR = 1.06, 95% CI = 0.96-1.17, p = 0.25). Similarly, in a meta-analysis which included the German association study (Münch, et al., 2005; 3092 ALS patients and 8215 controls) no association was found; although an increased frequency of H1/H1 in patients compared to controls was observed, this did not reach nominal significance (OR = 1.09, 95% CI = 0.99-1.19, p = 0.09).
To further elucidate the biological role of tau in ALS, we transgenically lowered tau expression levels in the SOD1G93A mouse by crossing this mouse with a mouse in which the MAPT gene has been deleted. Lower tau levels in transgenic SOD1G93A mice modestly increased survival of these mice (140.3 ± 12.5 days for SOD1G93A/MAPT+/+ mice, 150.5 ± 9.8 days for SOD1G93A/MAPT+/- mice and 146.2 ± 12.9 days for SOD1G93A/MAPT-/- mice; n = 12, 15 and 14 respectively), without changing the age of onset of the clinical motor deficits.
Our results demonstrate that tau doesn’t contribute to the pathogenesis of sporadic ALS in humans and of mutant SOD1-induced motor neuron degeneration in mice, in contrast to what has been found in other neurodegenerative diseases such as progressive supranuclear palsy (PSP) and Parkinson’s disease.
|Publication status: ||published|
|KU Leuven publication type: ||IMa|
|Appears in Collections:||Research Group Experimental Neurology |
Laboratory for Neurobiology (Vesalius Research Center)
Clinical Residents Medicine
Laboratory for Neuroimmunology
|Files in This Item:
There are no files associated with this item.