Interaction of alpha-synuclein and tau genotypes in Parkinson's disease.
To determine whether the microtubule-associated protein tau (MAPT) and alpha-synuclein (SNCA) genes interact to confer Parkinson's disease (PD) susceptibility, we conducted a study of 557 case-control pairs. There was an increased risk of PD for persons with either SNCA 261/261 or MAPT H1/H1 genotypes as compared with persons with neither (odds ratio, 1.96; 95% confidence interval, 1.34-2.86; p = 0.0003). However, the combined effect of the two genotypes was the same as for either of the genotypes alone (separate and equal). These findings are consistent with in vitro experiments that revealed tau-mediated fibrillization of alpha-synuclein protein at low concentrations (dose threshold effect).
Mamah
Catherine E
CE
Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Lesnick
Timothy G
TG
Lincoln
Sarah J
SJ
Strain
Kari J
KJ
de Andrade
Mariza
M
Bower
James H
JH
Ahlskog
J Eric
JE
Rocca
Walter A
WA
Farrer
Matthew J
MJ
Maraganore
Demetrius M
DM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016017:Odds Ratio; D010300:Parkinson Disease / Q000235:genetics*; D012306:Risk; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins / Q000235:genetics*
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins