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Kinesin gene variability may affect tau phosphorylation in early Alzheimer's disease

Author

  • Malin E. Andersson
  • Annica Sjolander
  • Niels Andreasen
  • Lennart Minthon
  • Oskar Hansson
  • Nenad Bogdanovic
  • Christina Jern
  • Katarina Jood
  • Anders Wallin
  • Kaj Blennow
  • Henrik Zetterberg

Summary, in English

Kinesin is a microtubule-associated motor protein that transports Alzheimer-associated amyloid precursor protein (APP) in neurons. In animal models, impaired kinesin-mediated APP transport seems to enhance formation of the neurotoxic 42 amino acid fragment of beta-amyloid (A beta 42). In man, one study suggests that a polymorphism (rs8702, 56,836G > C) in the kinesin light chain 1 gene (KNS2) may affect the risk of Alzheimer's disease (AD). To further assess KNS2 as a susceptibility gene for AD we analyzed 802 patients with sporadic AD and 286 controls, 134 longitudinally followed patients with mild cognitive impairment (MCI) and 39 cognitively stable controls for the rs8702 polymorphism. The rs8702 polymorphism did not influence risk of AD (p=0.46). However, rs8702 interacted with APOE epsilon 4 carrier status in AD (p=0.006) and influenced cerebrospinal fluid levels of hyper-phosphorylated tau in MCI patients who converted to AD during follow-up (p=0.018). These findings support earlier indications that genetic variability in the KNS2 gene may play a role during early stages of AD pathogenesis.

Publishing year

2007

Language

English

Pages

233-239

Publication/Series

International Journal of Molecular Medicine

Volume

20

Issue

2

Document type

Journal article

Publisher

Spandidos Publications

Topic

  • Neurology

Keywords

  • apolipoprotein
  • biomarkers
  • polymorphism
  • Alzheimer's disease
  • kinesin
  • E
  • axonal transport

Status

Published

Research group

  • Clinical Memory Research

ISBN/ISSN/Other

  • ISSN: 1791-244X