eprintid: 10110561
rev_number: 49
eprint_status: archive
userid: 608
dir: disk0/10/11/05/61
datestamp: 2020-09-23 10:03:57
lastmod: 2022-08-17 15:04:54
status_changed: 2021-04-27 10:33:00
type: article
metadata_visibility: show
creators_name: Keshavan, A
creators_name: Pannee, J
creators_name: Karikari, T
creators_name: Lantero Rodriguez, J
creators_name: Ashton, NJ
creators_name: Nicholas, JM
creators_name: Cash, D
creators_name: Coath, W
creators_name: Lane, CA
creators_name: Parker, TD
creators_name: Lu, K
creators_name: Buchanan, SM
creators_name: Keuss, SE
creators_name: James, SN
creators_name: Murray Smith, H
creators_name: Wong, A
creators_name: Barnes, A
creators_name: Dickson, JC
creators_name: Heslegrave, A
creators_name: Portelius, E
creators_name: Richards, M
creators_name: Fox, N
creators_name: Zetterberg, H
creators_name: Blennow, K
creators_name: Schott, J
title: Population-based blood screening for pre-clinical Alzheimer's disease in a British birth cohort at age 70
ispublished: pub
subjects: UCH
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F86
divisions: C10
divisions: D17
divisions: D14
divisions: GA3
divisions: G17
keywords: Alzheimer’s disease, amyloid imaging, dementia, beta-amyloid, tau, epidemiology
note: © The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
abstract: Alzheimer’s disease has a preclinical stage when cerebral amyloid-β deposition occurs before symptoms emerge, and when amyloid-β-targeted therapies may have maximum benefits. Existing amyloid-β status measurement techniques, including amyloid PET and CSF testing, are difficult to deploy at scale, so blood biomarkers are increasingly considered for screening. We compared three different blood-based techniques—liquid chromatography-mass spectrometry measures of plasma amyloid-β, and single molecule array (Simoa) measures of plasma amyloid-β and phospho-tau181—to detect cortical 18F-florbetapir amyloid PET positivity (defined as a standardized uptake value ratio of >0.61 between a predefined cortical region of interest and eroded subcortical white matter) in dementia-free members of Insight 46, a substudy of the population-based British 1946 birth cohort. We used logistic regression models with blood biomarkers as predictors of amyloid PET status, with or without age, sex and APOE ε4 carrier status as covariates. We generated receiver operating characteristics curves and quantified areas under the curves to compare the concordance of the different blood tests with amyloid PET. We determined blood test cut-off points using Youden’s index, then estimated numbers needed to screen to obtain 100 amyloid PET-positive individuals. Of the 502 individuals assessed, 441 dementia-free individuals with complete data were included; 82 (18.6%) were amyloid PET-positive. The area under the curve for amyloid PET status using a base model comprising age, sex and APOE ε4 carrier status was 0.695 (95% confidence interval: 0.628–0.762). The two best-performing Simoa plasma biomarkers were amyloid-β42/40 (0.620; 0.548–0.691) and phospho-tau181 (0.707; 0.646–0.768), but neither outperformed the base model. Mass spectrometry plasma measures performed significantly better than any other measure (amyloid-β1-42/1-40: 0.817; 0.770–0.864 and amyloid-β composite: 0.820; 0.775–0.866). At a cut-off point of 0.095, mass spectrometry measures of amyloid-β1-42/1-40 detected amyloid PET positivity with 86.6% sensitivity and 71.9% specificity. Without screening, to obtain 100 PET-positive individuals from a population with similar amyloid PET positivity prevalence to Insight 46, 543 PET scans would need to be performed. Screening using age, sex and APOE ε4 status would require 940 individuals, of whom 266 would proceed to scan. Using mass spectrometry amyloid-β1-42/1-40 alone would reduce these numbers to 623 individuals and 243 individuals, respectively. Across a theoretical range of amyloid PET positivity prevalence of 10–50%, mass spectrometry measures of amyloid-β1-42/1-40 would consistently reduce the numbers proceeding to scans, with greater cost savings demonstrated at lower prevalence.
date: 2021-02
date_type: published
publisher: Oxford University Press (OUP)
official_url: http://dx.doi.org/10.1093/brain/awaa403
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1814915
doi: 10.1093/brain/awaa403
lyricists_name: Buchanan, Sarah
lyricists_name: Cash, David
lyricists_name: Coath, William
lyricists_name: Dickson, John
lyricists_name: Fox, Nicholas
lyricists_name: Heslegrave, Amanda
lyricists_name: James, Sarah
lyricists_name: Keshavan, Ashvini
lyricists_name: Keuss, Sarah
lyricists_name: Lu, Kirsty
lyricists_name: Parker, Thomas
lyricists_name: Richards, Marcus
lyricists_name: Schott, Jonathan
lyricists_name: Wong, Andrew
lyricists_name: Zetterberg, Henrik
lyricists_id: SMBUC64
lyricists_id: DMCAS28
lyricists_id: WOCOA32
lyricists_id: JCDIC92
lyricists_id: NCIFO25
lyricists_id: AJHES09
lyricists_id: SNJAM11
lyricists_id: AKESH31
lyricists_id: SEKEU60
lyricists_id: KMACP41
lyricists_id: TPARK85
lyricists_id: MRICH78
lyricists_id: JMSCH12
lyricists_id: AWKWO84
lyricists_id: HZETT94
actors_name: Allington-Smith, Dominic
actors_id: DAALL44
actors_role: owner
full_text_status: public
publication: Brain
volume: 144
number: 2
pagerange: 434-449
citation:        Keshavan, A;    Pannee, J;    Karikari, T;    Lantero Rodriguez, J;    Ashton, NJ;    Nicholas, JM;    Cash, D;                                                                         ... Schott, J; + view all <#>        Keshavan, A;  Pannee, J;  Karikari, T;  Lantero Rodriguez, J;  Ashton, NJ;  Nicholas, JM;  Cash, D;  Coath, W;  Lane, CA;  Parker, TD;  Lu, K;  Buchanan, SM;  Keuss, SE;  James, SN;  Murray Smith, H;  Wong, A;  Barnes, A;  Dickson, JC;  Heslegrave, A;  Portelius, E;  Richards, M;  Fox, N;  Zetterberg, H;  Blennow, K;  Schott, J;   - view fewer <#>    (2021)    Population-based blood screening for pre-clinical Alzheimer's disease in a British birth cohort at age 70.                   Brain , 144  (2)   pp. 434-449.    10.1093/brain/awaa403 <https://doi.org/10.1093/brain%2Fawaa403>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10110561/9/Population-based%20blood%20screening%20for%20preclinical%20Alzheimers%20disease%20in%20a%20British%20birth%20cohort%20at%20age%2070.pdf