Blood-based biomarker candidates of cerebral amyloid using PiB PET in non-demented elderly

Westwood, Sarah, Leoni, Emanuela, Hye, Abdul, Lynham, Steven, Khondoker, Mizanur R. ORCID: https://orcid.org/0000-0002-1801-1635, Ashton, Nicholas J., Kiddle, Steven J., Baird, Alison L., Sainz-Fuertes, Ricardo, Leung, Rufina, Graf, John, Hehir, Cristina Tan, Baker, David, Cereda, Cristina, Bazenet, Chantal, Ward, Malcolm, Thambisetty, Madhav and Lovestone, Simon (2016) Blood-based biomarker candidates of cerebral amyloid using PiB PET in non-demented elderly. Journal of Alzheimer's Disease, 52 (2). pp. 561-572. ISSN 1387-2877

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Abstract

Increasingly, clinical trials for Alzheimer’s disease (AD) are being conducted earlier in the disease phase and with biomarker confirmation using in vivo amyloid PET imaging or CSF tau and Aβ measures to quantify pathology. However, making such a pre-clinical AD diagnosis is relatively costly and the screening failure rate is likely to be high. Having a blood-based marker that would reduce such costs and accelerate clinical trials through identifying potential participants with likely pre-clinical AD would be a substantial advance. In order to seek such a candidate biomarker, discovery phase proteomic analyses using 2DGE and gel-free LC-MS/MS for high and low molecular weight analytes were conducted on longitudinal plasma samples collected over a 12-year period from non-demented older individuals who exhibited a range of 11C-PiB PET measures of amyloid load. We then sought to extend our discovery findings by investigating whether our candidate biomarkers were also associated with brain amyloid burden in disease, in an independent cohort. Seven plasma proteins, including A2M, Apo-A1, and multiple complement proteins, were identified as pre-clinical biomarkers of amyloid burden and were consistent across three time points (p <  0.05). Five of these proteins also correlated with brain amyloid measures at different stages of the disease (q <  0.1). Here we show that it is possible to detect a plasma based biomarker signature indicative of AD pathology at a stage long before the onset of clinical disease manifestation. As in previous studies, acute phase reactants and inflammatory markers dominate this signature.

Item Type:	Article
Uncontrolled Keywords:	alzheimer's disease,amyloid,biological markers,blood,plasma,preclinical,proteomics
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Epidemiology and Public Health Faculty of Medicine and Health Sciences > Research Groups > Public Health and Health Services Research (former - to 2023) Faculty of Science > Research Groups > Norwich Epidemiology Centre Faculty of Medicine and Health Sciences > Research Groups > Norwich Epidemiology Centre Faculty of Medicine and Health Sciences > Research Centres > Population Health
Depositing User:	Pure Connector
Date Deposited:	24 Sep 2016 00:24
Last Modified:	19 Oct 2023 01:45
URI:	https://ueaeprints.uea.ac.uk/id/eprint/60030
DOI:	10.3233/JAD-151155

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