Kinesin gene variability may affect tau phosphorylation in early Alzheimer's disease
Author
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.
Department/s
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