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Title: | Impact of APOE-ε4 carriage on the onset and rates of neocortical Aβ-amyloid deposition. | Austin Authors: | Burnham, Samantha C;Laws, Simon M;Budgeon, Charley A;Doré, Vincent ;Porter, Tenielle;Bourgeat, Pierrick;Buckley, Rachel F;Murray, Kevin;Ellis, Kathryn A;Turlach, Berwin A;Salvado, Olivier;Ames, David;Martins, Ralph N;Rentz, Dorene;Masters, Colin L ;Rowe, Christopher C ;Villemagne, Victor L | Affiliation: | eHealth, CSIRO Health and Biosecurity, Floreat, Western Australia, Australia Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia Cooperative Research Centre for Mental Health, http://www.mentalhealthcrc.com, Perth, Western Australia, Australia School of Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, Western Australia, Australia Collaborative Genomics Group, Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia eHealth, CSIRO Health and Biosecurity, Parkville, Victoria, Australia Medicine (University of Melbourne) Molecular Imaging and Therapy National Ageing Research Institute, Parkville, Victoria, Australia University of Melbourne Academic Unit for Psychiatry of Old Age, St George's Hospital, Kew, Victoria, Australia Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Melbourne School of Psychological Sciences, University of Melbourne, Parkville, Victoria, Australia Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia Centre for Applied Statistics, University of Western Australia, Crawley, Western Australia, Australia Academic Unit for Psychiatry of Old Age, Department of Psychiatry, University of Melbourne, Parkville, Victoria, Australia School of Population and Global Health, University of Western Australia, Crawley, Western Australia, Australia eHealth, CSIRO Health and Biosecurity, Herston, Queensland, Australia Florey Institute, University of Melbourne, Parkville, Victoria, Australia Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia |
Issue Date: | Nov-2020 | Date: | 2020-06-10 | Publication information: | Neurobiology of Aging 2020; 95: 46-55 | Abstract: | 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. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/24522 | DOI: | 10.1016/j.neurobiolaging.2020.06.001 | Journal: | Neurobiology of Aging | PubMed URL: | 32750666 | Type: | Journal Article | Subjects: | APOE Alzheimer's disease Aβ-amyloid Biomarkers Longitudinal |
Appears in Collections: | Journal articles |
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