Brain Amyloid in Sporadic Young Onset Alzheimer's Disease

Background: Controversy exists as to the role of the amyloid-beta (A beta) peptide in the pathophysiology of Alzheimer's disease (AD). Objective: To clarify the effect of age on A beta deposition in sporadic AD by exploring the degree of amyloid burden in patients with sporadic young onset AD (YOAD). Methods: Patients were diagnosed with YOAD with dementia starting before the age of 65 years (N = 42; males = 20, females = 22). A cross-sectional analysis of amyloid binding using positron emission tomography (PET) imaging was performed using the C-Pittsburgh Compound B (PiB). The global standardized uptake value ratios (gSUVR) were examined using the Wilcoxon two-sample test, as were the cognitive scores between disease and healthy control populations. Differences in PiB retention in different anatomical areas were compared using the Kruskal-Wallis test. The contrast in APOE genotyping between groups was calculated with Fisher's Exact Test. Results: Women had a mediangSUVR = 2.68 +/- 0.73 and73% had at least oneAPOE epsilon 4 allele. MenhadgSUVR = 2.37 +/- 0.54, with 80% having at least one APOE epsilon 4 allele. The gSUVRs were significantly higher than the control populations for men and women and had significantly greater frequency of APOE epsilon 4. Men and women analyzed together had significantly greater amyloid burden and APOE epsilon 4 allele frequencies than controls, but no differences existed between them in gSUVR nor in the anatomical distribution of amyloid uptake. Conclusion: Men and women with YOAD have greater amyloid uptake than controls and have more APOE epsilon 4 alleles. Our findings suggest that the A beta peptide is operational in young onset dementia and driven by the APOE epsilon 4 allele.