A blood-based predictor for neocortical Aβ burden in Alzheimer's disease: results from the AIBL study

被引:99
作者
Burnham, S. C. [1 ]
Faux, N. G. [2 ]
Wilson, W. [3 ]
Laws, S. M. [4 ,5 ]
Ames, D. [6 ,7 ]
Bedo, J. [8 ]
Bush, Ai [2 ]
Doecke, J. D. [9 ]
Ellis, K. A. [6 ]
Head, R. [10 ]
Jones, G. [11 ,12 ,13 ]
Kiiveri, H. [1 ]
Martins, R. N. [4 ,5 ]
Rembach, A. [2 ]
Rowe, C. C. [11 ,12 ,13 ]
Salvado, O. [14 ]
Macaulay, S. L. [15 ]
Masters, C. L. [2 ]
Villemagne, V. L. [11 ,12 ]
机构
[1] CSIRO Preventat Hlth Flagship Math Informat & Sta, Perth, WA, Australia
[2] Univ Melbourne, Mental Hlth Res Inst MHRI, Parkville, Vic 3052, Australia
[3] CSIRO Preventat Hlth Flagship Math Informat & Sta, N Ryde, NSW, Australia
[4] Edith Cowan Univ, Sch Med Sci, Ctr Excellence Alzheimers Dis Res & Care, Joondalup, WA, Australia
[5] Hollywood Private Hosp, Sir James McCusker Alzheimers Dis Res Unit, Perth, WA, Australia
[6] Univ Melbourne, Dept Psychiat, Acad Unit Psychiat Old Age, Parkville, Vic 3052, Australia
[7] Natl Ageing Res Inst, Parkville, Vic, Australia
[8] Natl ICT Australia NICTA, Victorian Res Lab, Melbourne, Vic, Australia
[9] CSIRO Preventat Hlth Flagship Math Informat & Sta, Herston, Qld, Australia
[10] CSIRO Preventat Hlth Flagship Hlth & Life Sci, Urrbrae, SA, Australia
[11] Austin Hlth, Dept Nucl Med, Heidelberg, Vic, Australia
[12] Austin Hlth, Ctr PET, Heidelberg, Vic, Australia
[13] Univ Melbourne, Dept Med, Austin Hlth, Heidelberg, Vic, Australia
[14] CSIRO Preventat Hlth Flagship Informat & Commun T, Herston, Qld, Australia
[15] CSIRO Preventat Hlth Flagship Mat Sci & Engn, Parkville, Vic, Australia
基金
英国医学研究理事会; 美国国家卫生研究院; 加拿大健康研究院; 澳大利亚国家健康与医学研究理事会;
关键词
Alzheimer's disease; amyloid beta; blood biomarkers; MILD COGNITIVE IMPAIRMENT; PLASMA AMYLOID-BETA; ASSOCIATION WORKGROUPS; PANCREATIC-POLYPEPTIDE; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; NONDEMENTED INDIVIDUALS; CEREBROSPINAL-FLUID; APOLIPOPROTEIN-E; WORKING GROUP;
D O I
10.1038/mp.2013.40
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Dementia is a global epidemic with Alzheimer's disease (AD) being the leading cause. Early identification of patients at risk of developing AD is now becoming an international priority. Neocortical A beta (extracellular beta-amyloid) burden (NAB), as assessed by positron emission tomography (PET), represents one such marker for early identification. These scans are expensive and are not widely available, thus, there is a need for cheaper and more widely accessible alternatives. Addressing this need, a blood biomarker-based signature having efficacy for the prediction of NAB and which can be easily adapted for population screening is described. Blood data (176 analytes measured in plasma) and Pittsburgh Compound B (PiB)-PET measurements from 273 participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study were utilised. Univariate analysis was conducted to assess the difference of plasma measures between high and low NAB groups, and cross-validated machine-learning models were generated for predicting NAB. These models were applied to 817 non-imaged AIBL subjects and 82 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) for validation. Five analytes showed significant difference between subjects with high compared to low NAB. A machine-learning model (based on nine markers) achieved sensitivity and specificity of 80 and 82%, respectively, for predicting NAB. Validation using the ADNI cohort yielded similar results (sensitivity 79% and specificity 76%). These results show that a panel of blood-based biomarkers is able to accurately predict NAB, supporting the hypothesis for a relationship between a blood-based signature and A beta accumulation, therefore, providing a platform for developing a population-based screen.
引用
收藏
页码:519 / 526
页数:8
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