Association of the tau haplotype H2 with age at onset and functional alterations of glucose utilization in frontotemporal dementia.
OBJECTIVE
The microtubule-associated protein tau gene (MAPT) contains two extended haplotypes, H1 and H2, which have been linked with sporadic tauopathies. However, there is little evidence as to how these haplotypes may influence the clinical features of the disease. The aim of this study was to investigate the MAPT haplotypes in relation to risk for, and functional alterations of glucose metabolism in, patients with frontotemporal dementia (FTD).


METHODS
The authors investigated MAPT haplotypes in 142 individuals with FTD and 292 comparison subjects. Additionally, in a subset of 41 individuals with FTD and 16 comparison subjects, the authors undertook functional [ (18)F]fluorodeoxyglucose positron emission tomography (PET) imaging.


RESULTS
MAPT haplotype distribution did not differ significantly between individuals with FTD and comparison subjects. However, the H2 haplotype was clinically associated with an earlier age at onset of FTD, which presented in a dose-dependent manner. Correspondingly, PET analysis revealed functional differences in glucose utilization patterns between MAPT haplotypes, with H2 carriers having a more pronounced hypometabolism in frontal brain areas than H1 carriers, which could not be accounted for by differences in duration of illness.


CONCLUSIONS
While the extended MAPT H1 and H2 haplotypes do not appear to confer risk for disease development, the H2 haplotype appears to modify age at onset and functionally shows a more severe decline of glucose utilization in frontal brain areas.
Laws
Simon M
SM
Neurochemistry and Neurogenetics Laboratory, Department of Psychiatry and Psychotherapy, Munich University of Technology, 81675 Munich, Germany.
Perneczky
Robert
R
Drzezga
Alexander
A
Diehl-Schmid
Janine
J
Ibach
Bernd
B
Bäuml
Josef
J
Eisele
Tamara
T
Förstl
Hans
H
Kurz
Alexander
A
Riemenschneider
Matthias
M
D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003704:Dementia / Q000235:genetics* / Q000378:metabolism; D019788:Fluorodeoxyglucose F18; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D005947:Glucose / Q000378:metabolism*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D012307:Risk Factors; D024801:Tauopathies / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics*
C054369:MAPT protein, human; D016875:tau Proteins; D019788:Fluorodeoxyglucose F18; D005947:Glucose