Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease.
OBJECTIVE
Cerebral parietal hypometabolism and left-right asymmetry occur early in the course of Alzheimer disease (AD), and the apolipoprotein E type 4 allele (APOE epsilon 4) is a risk factor for familial AD. To determine if APOE epsilon 4 is associated with lowered brain function in nondemented relatives at risk for familial AD, we studied 12 relatives with APOE epsilon 4 and 19 relatives without APOE epsilon 4. We also compared them with seven patients with probable AD.


METHODS
After grouping subjects according to diagnosis and genotype, brain function measures were compared among groups.


METHODS
University medical center.


METHODS
At risk subjects had mild memory complaints, normal cognitive performance, and at least two relatives with AD. Subjects with APOE epsilon 4 did not differ from those without APOE epsilon 4 in mean age at examination (56.4 vs 55.5 years) or in neuropsychological performance (mean Mini-Mental State Examination score, 28.8 vs 29.3).


METHODS
Cerebral glucose metabolism was measured using positron emission tomography and fludeoxyglucose F 18.


RESULTS
Parietal metabolism was significantly lower and left-right parietal asymmetry was significantly higher in at-risk subjects with APOE epsilon 4 compared with those without APOE epsilon 4. Patients with dementia had significantly lower parietal metabolism than did at-risk subjects with APOE epsilon 4.


CONCLUSIONS
These results suggest that the inheritance of APOE epsilon 4 is associated with reduced cerebral parietal metabolism and increased asymmetry in non-demented relatives at risk for probable AD. Longitudinal study will determine if glucose metabolic measures provide a means to monitor experimental treatment responses during the early phases of the disorder.
Small
G W
GW
Department of Psychiatry, University of California, Los Angeles School of Medicine.
Mazziotta
J C
JC
Collins
M T
MT
Baxter
L R
LR
Phelps
M E
ME
Mandelkern
M A
MA
Kaplan
A
A
La Rue
A
A
Adamson
C F
CF
Chang
L
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D000704:Analysis of Variance; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D003847:Deoxyglucose / Q000031:analogs & derivatives; D005190:Family; D005260:Female; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D005838:Genotype; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D009483:Neuropsychological Tests; D012307:Risk Factors; D014055:Tomography, Emission-Computed
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D003847:Deoxyglucose; D005947:Glucose