Regional cerebral glucose utilization is modulated by the dosage of apolipoprotein E type 4 allele and alpha1-antichymotrypsin type A allele in Alzheimer's disease.
Twenty Alzheimer's disease (AD) patients with defined apolipoprotein E (APOE), alpha1-antichymotrypsin (ACT) and presenilin-1 (PS-1) intronic genotypes were examined to quantify the regional cerebral metabolic rate of glucose (rCMRglc) using positron emission tomography (PET) and 18F-2-fluoro-2-deoxy-D-glucose (FDG). The frontal rCMRglc was significantly increased in patients with the APOE epsilon4 allele in a dose-dependent fashion. In contrast, the temporo-parietal rCMRglc was significantly reduced in ACT type A allele (ACT*A) carriers compared with those in non-ACT*A carriers. The PS-1 type 1 intronic allele had no significant effects on rCMRglc in any cerebral region. These results suggest that both the APOE and ACT genes may play a distinct role in the progression of AD as monitored by imaging studies of cerebral glucose utilization.
Higuchi
M
M
Department of Geriatric Medicine, Tohoku University School of Medicine, Sendai, Japan.
Arai
H
H
Nakagawa
T
T
Higuchi
S
S
Muramatsu
T
T
Matsushita
S
S
Kosaka
Y
Y
Itoh
M
M
Sasaki
H
H
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D018628:Gene Dosage; D005838:Genotype; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D053764:Presenilin-1; D012307:Risk Factors; D014055:Tomography, Emission-Computed; D000514:alpha 1-Antichymotrypsin / Q000235:genetics*
D001057:Apolipoproteins E; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D000514:alpha 1-Antichymotrypsin; D005947:Glucose