Kinesin gene variability may affect tau phosphorylation in early Alzheimer's disease.
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 hyperphosphorylated 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.
Andersson
Malin E
ME
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
Sjölander
Annica
A
Andreasen
Niels
N
Minthon
Lennart
L
Hansson
Oskar
O
Bogdanovic
Nenad
N
Jern
Christina
C
Jood
Katarina
K
Wallin
Anders
A
Blennow
Kaj
K
Zetterberg
Henrik
H
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation / Q000502:physiology; D006801:Humans; D016547:Kinesins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D010766:Phosphorylation; D020641:Polymorphism, Single Nucleotide; D011494:Protein Kinases / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D001057:Apolipoproteins E; D008869:Microtubule-Associated Proteins; D016875:tau Proteins; D011494:Protein Kinases; D016547:Kinesins