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.

Automated summary

This study found differential effects of APOE ε4 on the relationship between tau and amyloid in patients with early-onset and late-onset Alzheimer's disease. Early-onset Alzheimer's disease ε4- patients showed more tau retention in the association cortices, while ε4+ patients had more retention in the medial temporal areas. The tau topography of late-onset Alzheimer's disease ε4+ was similar to that of early-onset Alzheimer's disease ε4+.