Metabolic interaction between ApoE genotype and onset age in Alzheimer's disease: implications for brain reserve.
BACKGROUND
Clinically apparent Alzheimer's disease (AD) is thought to result when brain tissue damage exceeds a critical threshold of "brain reserve", a process possibly accelerated by the apolipoprotein E (ApoE) E4 allele. The interaction between onset age and ApoE genotype was investigated to assess whether early disease onset (<65 years) in patients carrying the E4 allele is associated with greater cerebral metabolic (regional cerebral metabolic rate of glucose utilisation, rCMRgl) reduction.


METHODS
AD patients, divided into early (EOAD; 27 patients) and late onset (LOAD; 65 patients) groups, both groups balanced as to the number of E4 carriers (E4+) and non-carriers (E4-), and matched controls (NC; 35 cases) underwent (18)F-FDG PET ([(18)F]fluorodeoxyglucose positron emission tomography) scanning. SPM'99 software was used to compare AD patients to NC and to perform a two way ANOVA with onset age and ApoE genotype as grouping factors. Results were considered significant at p<0.001, uncorrected.


RESULTS
AD patients demonstrated rCMRgl reductions compared to NC, with rCMRgl lower in association cortex and relatively higher in limbic areas in EOAD compared to LOAD subjects. rCMRgl was lower in the anterior cingulate and frontal cortex for E4+ compared to E4- subjects. A significant onset age by ApoE interaction was detected in the hippocampi and basal frontal cortex, with EOAD E4+ subjects having the greatest rCMRgl reduction.


CONCLUSIONS
The interactive effects of early onset age, possibly reflecting lower brain reserve, and ApoE E4 allele, possibly leading to greater tissue damage, lead to reduced tolerance to the pathophysiological effects of AD in key brain regions.
Mosconi
L
L
Department of Clinical Pathophysiology, Nuclear Medicine Unit, University of Florence, viale Morgagni 85, 50134 Florence, Italy.
Herholz
K
K
Prohovnik
I
I
Nacmias
B
B
De Cristofaro
M T R
MT
Fayyaz
M
M
Bracco
L
L
Sorbi
S
S
Pupi
A
A
D017668:Age of Onset; 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*; D016022:Case-Control Studies; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics
D001057:Apolipoproteins E; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18