Effects of the APOE ε4 Allele on the Relationship Between Tau and Amyloid-β in Early- and Late-Onset Alzheimer's Disease

Background: Little is known regarding the differential effects of the apolipoprotein E (APOE) epsilon 4 on the regional topography of amyloid and tau in patients with both early-onset (EOAD) and late-onset Alzheimer's disease (LOAD). Objective: To compare the distribution and association of tau, amyloid, and cortical thickness among groups classified by the presence of APOE epsilon 4 allele and onset age. Methods: A total of 165 participants including 54 EOAD patients (29 epsilon 4-; 25 epsilon 4+), 45 LOAD patients (21 epsilon 4-; 24 epsilon 4+), and 66 age-matched controls underwent 3T MRI, F-18-THK5351 (THK) and F-18-flutemetamol (FLUTE) PET scans, APOE genotyping, and neuropsychological tests. Data for voxel-wise and standardized uptake values from PET scans were analyzed in the context of APOE and age at onset. Results: EOAD epsilon 4- patients showed greater THK retention in the association cortices, whereas their EOAD epsilon 4+ counterparts had more retention in medial temporal areas. THK topography of LOAD epsilon 4+ was similar to EOAD epsilon 4 +. THK correlated positively with FLUTE and conversely with mean cortical thickness, being lowest in EOAD epsilon 4-, highest in LOAD epsilon 4-, and modest in epsilon 4+ groups. Even in the APOE epsilon 4+ groups, THK tended to correlate with FLUTE and mean cortical thickness in the inferior parietal region in EOAD and in the medial temporal region in LOAD. LOAD epsilon 4- manifested with prevalent small vessel disease markers and the lowest correlation between THK retention and cognition. Conclusion: Our observations suggest the differential effects of the APOE epsilon 4 on the relationship between tau and amyloid in EOAD and LOAD.