Impact of APOE-ε4 carriage on the onset and rates of neocortical Aβ-amyloid deposition

Authors/Creators

• Samantha C. Burnham, Edith Cowan UniversityFollow
• Simon M. Laws, Edith Cowan UniversityFollow
• Charley A. Budgeon
• Vincent Doré
• Tenielle Porter, Edith Cowan UniversityFollow
• Pierrick Bourgeat
• Rachel F. Buckley
• Kevin Murray
• Kathryn A. Ellis
• Berwin A. Turlach
• Olivier Salvado
• David Ames
• Ralph N. Martins, Edith Cowan UniversityFollow
• Dorene Rentz
• Colin L. Masters
• Christopher C. Rowe
• Victor L. Villemagne
• Alzheimer's Disease Neuroimaging Inititive
• Australian Imaging, Biomarker & Lifestyle Research Group

Abstract

© 2020 Elsevier Inc. Neocortical Aβ-amyloid deposition, one of the hallmark pathologic features of Alzheimer's disease (AD), begins decades prior to the presence of clinical symptoms. As clinical trials move to secondary and even primary prevention, understanding the rates of neocortical Aβ-amyloid deposition and the age at which Aβ-amyloid deposition becomes abnormal is crucial for optimizing the timing of these trials. As APOE-ε4 carriage is thought to modulate the age of clinical onset, it is also important to understand the impact of APOE-ε4 carriage on the age at which the neocortical Aβ-amyloid deposition becomes abnormal. Here, we show that, for 455 participants with over 3 years of follow-up, abnormal levels of neocortical Aβ-amyloid were reached on average at age 72 (66.5–77.1). The APOE-ε4 carriers reached abnormal levels earlier at age 63 (59.6–70.3); however, noncarriers reached the threshold later at age 78 (76.1–84.4). No differences in the rates of deposition were observed between APOE-ε4 carriers and noncarriers after abnormal Aβ-amyloid levels had been reached. These results suggest that primary and secondary prevention trials, looking to recruit at the earliest stages of disease, should target APOE-ε4 carriers between the ages of 60 and 66 and noncarriers between the ages of 76 and 84.

Keywords

Alzheimer's disease, APOE, Aβ-amyloid, Biomarkers, Longitudinal

Document Type

Journal Article

Date of Publication

11-1-2020

ISSN

01974580

Volume

95

PubMed ID

32750666

Publication Title

Neurobiology of Aging

Publisher

Elsevier

School

Centre of Excellence for Alzheimer's Disease Research and Care / School of Medical and Health Sciences

RAS ID

32043

Comments

Burnham, S. C., Laws, S. M., Budgeon, C. A., Doré, V., Porter, T., Bourgeat, P., ... & Villemagne, V. L. (2020). Impact of APOE-ε4 carriage on the onset and rates of neocortical Aβ-amyloid deposition. Neurobiology of Aging, 95, 46-55. https://doi.org/10.1016/j.neurobiolaging.2020.06.001

Copyright

subscription content

First Page

46

Last Page

55