title: Tau levels do not influence human ALS or motor neuron degeneration in the SOD1G93A mouse.
abstract: BACKGROUND
  The microtubule-associated protein tau is thought to play a pivotal role in neurodegeneration. Mutations in the tau coding gene MAPT are a cause of frontotemporal dementia, and the H1/H1 genotype of MAPT, giving rise to higher tau expression levels, is associated with progressive supranuclear palsy, corticobasal degeneration, and Parkinson disease (PD). Furthermore, tau hyperphosphorylation and aggregation is a hallmark of Alzheimer disease (AD), and reducing endogenous tau has been reported to ameliorate cognitive impairment in a mouse model for AD. Tau hyperphosphorylation and aggregation have also been described in amyotrophic lateral sclerosis (ALS), both in human patients and in the mutant SOD1 mouse model for this disease. However, the precise role of tau in motor neuron degeneration remains uncertain.
  
  
  METHODS
  The possible association between ALS and the MAPT H1/H2 polymorphism was studied in 3,540 patients with ALS and 8,753 controls. Furthermore, the role of tau in the SOD1(G93A) mouse model for ALS was studied by deleting Mapt in this model.
  
  
  RESULTS
  The MAPT genotype of the H1/H2 polymorphism did not influence ALS susceptibility (odds ratio = 1.08 [95% confidence interval 0.99-1.18], p = 0.08) and did not affect the clinical phenotype. Lowering tau levels in the SOD1(G93A) mouse failed to delay disease onset (p = 0.302) or to increase survival (p = 0.557).
  
  
  CONCLUSIONS
  These findings suggest that the H1/H2 polymorphism in MAPT is not associated with human amyotrophic lateral sclerosis, and that lowering tau levels in the mutant SOD1 mouse does not affect the motor neuron degeneration in these animals.
authors.affiliation: Laboratory of Neurobiology and Department of Neurology, University Hospital Gasthuisberg, K.U. Leuven, Leuven, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Taes
authors.forename: A
authors.initials: A
authors.lastname: Goris
authors.forename: R
authors.initials: R
authors.lastname: Lemmens
authors.forename: M A
authors.initials: MA
authors.lastname: van Es
authors.forename: L H
authors.initials: LH
authors.lastname: van den Berg
authors.forename: A
authors.initials: A
authors.lastname: Chio
authors.forename: B J
authors.initials: BJ
authors.lastname: Traynor
authors.forename: A
authors.initials: A
authors.lastname: Birve
authors.forename: P
authors.initials: P
authors.lastname: Andersen
authors.forename: A
authors.initials: A
authors.lastname: Slowik
authors.forename: B
authors.initials: B
authors.lastname: Tomik
authors.forename: R H
authors.initials: RH
authors.lastname: Brown
authors.forename: C E
authors.initials: CE
authors.lastname: Shaw
authors.forename: A
authors.initials: A
authors.lastname: Al-Chalabi
authors.forename: S
authors.initials: S
authors.lastname: Boonen
authors.forename: L
authors.initials: L
authors.lastname: Van Den Bosch
authors.forename: B
authors.initials: B
authors.lastname: Dubois
authors.forename: P
authors.initials: P
authors.lastname: Van Damme
authors.forename: W
authors.initials: W
authors.lastname: Robberecht
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D000704:Analysis of Variance; D000818:Animals; D015331:Cohort Studies; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism*; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C000606290:SOD1 protein, human; C485184:enhanced green fluorescent protein; D016875:tau Proteins; D049452:Green Fluorescent Proteins; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1