Increased risk for frontotemporal dementia through interaction between tau polymorphisms and apolipoprotein E epsilon4.
The tau gene has an important role in frontotemporal dementia (FTD) as pathogenic mutations have been found in hereditary forms of the disease. Furthermore, a certain extended tau haplotype has been shown to increase the risk for progressive supranuclear palsy, corticobasal degeneration, Parkinson's disease and, in interaction with the apolipoprotein E (apoE) epsilon4 allele, Alzheimer's disease. By microsatellite analysis we investigated an intronic tau polymorphism, in linkage disequilibrium with the extended tau haplotype, in FTD patients (n = 36) and healthy controls (n = 39). No association between any of the tau alleles/genotypes and FTD was seen, but certain tau alleles and apoE epsilon4 interactively increased the risk of FTD (p = 0.006). We thus propose that this extended tau haplotype in combination with apoE epsilon4 is a genetic risk factor for FTD.
Ingelson
M
M
Karolinska Institutet, NEUROTEC, Novum, KFC, Huddinge, Sweden.
Fabre
S F
SF
Lilius
L
L
Andersen
C
C
Viitanen
M
M
Almkvist
O
O
Wahlund
L O
LO
Lannfelt
L
L
D000368:Aged; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D003704:Dementia / Q000235:genetics* / Q000473:pathology; D005260:Female; D005625:Frontal Lobe; D008040:Genetic Linkage / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D013702:Temporal Lobe; D016875:tau Proteins / Q000235:genetics*
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D016875:tau Proteins