Abstract
BackgroundWhen Alzheimer’s disease (AD) is occurring at an early onset before 65 years old, its clinical course is generally more aggressive than in the case of a late onset. We aim at identifying [^{18}F]florbetaben PET biomarkers sensitive to differences between early-onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD). We conducted [^{18}F]florbetaben PET/CT scans of 43 newly diagnosed AD subjects. We calculated 93 textural parameters for each of the 83 Hammers areas. We identified 41 independent principal components for each brain region, and we studied their Spearman correlation with the age of AD onset, by taking into account multiple comparison corrections. Finally, we calculated the probability that EOAD and LOAD patients have different amyloid-beta (Abeta) deposition by comparing the mean and the variance of the significant principal components obtained in the two groups with a 2-tailed Student’s t-test.ResultsWe found that four principal components exhibit a significant correlation at a 95% confidence level with the age of onset in the left lateral part of the anterior temporal lobe, the right anterior orbital gyrus of the frontal lobe, the right lateral orbital gyrus of the frontal lobe and the left anterior part of the superior temporal gyrus. The data are consistent with the hypothesis that EOAD patients have a significantly different [^{18}F]florbetaben uptake than LOAD patients in those four brain regions.ConclusionsEarly-onset AD implies a very irregular pattern of Abeta deposition. The authors suggest that the identified textural features can be used as quantitative biomarkers for the diagnosis and characterization of EOAD patients.
Highlights
When Alzheimer’s disease (AD) is occurring at an early onset before 65 years old, its clinical course is generally more aggressive than in the case of a late onset
For a more quantitative estimation of the level of significance, we report in Figs. 4c, d and 5c, d the P-value of the Student’s t-test applied to the distribution of the four principal components in the left lateral part of the anterior temporal lobe, the right anterior orbital gyrus of the frontal lobe, the right lateral orbital gyrus of the frontal lobe and the left anterior part of the superior temporal gyrus corresponding to early-onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD) patients defined with an age of onset threshold A
10, 5 significant correlation of any first-order statistical characteristics of the Standardized Uptake Value (SUV) distribution and age of onset of AD, we found four independent principal components in the left lateral part of the anterior temporal lobe, the right anterior orbital gyrus of the frontal lobe, the right lateral orbital gyrus of the frontal lobe and the left anterior part of the superior temporal gyrus exhibiting a significant correlation with the age of onset of AD
Summary
When Alzheimer’s disease (AD) is occurring at an early onset before 65 years old, its clinical course is generally more aggressive than in the case of a late onset. We aim at identifying [1 8F]florbetaben PET biomarkers sensitive to differences between early-onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD). We calculated the probability that EOAD and LOAD patients have different amyloid-β ( Aβ ) deposition by comparing the mean and the variance of the significant principal components obtained in the two groups with a 2-tailed Student’s t-test. The most promising approaches involve, on the one hand, the detection of soluble biomarkers in the cerebrospinal fluid and, on the other hand, the molecular imaging of glucose metabolism, Aβ and tau accumulation in the brain cortex with positron emission tomography (PET). While differences in cerebral metabolic impairment between EAOD and LOAD were observed and supported by histopathological findings [15, 16], suggesting the existence of biological subtypes of AD, the Aβ deposition seems not to be correlated with the age of onset of AD [17]
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