OUP accepted manuscript

• DOI: 10.1093/brain/awaa403
• Publication Date: 2020-11-04T20:21:24Z
• Authors: Ashvini Keshavan; Josef Pannee; Thomas K. Karikari; Juan Lantero Rodr...; Nicholas J. Ashton; Jennifer Nicholas; David M. Cash; William Coath; Christopher Lane; Thomas D. Parker; Kirsty Lu; Sarah M. Buchanan; Sarah E Keuss; Sarah‐Naomi James; Heidi Murray‐Smith; Andrew Wong; Anna Barnes; John Dickson; Amanda Heslegrave; Erik Portelius; Marcus Richards; Nick C. Fox; Henrik Zetterberg; Kaj Blennow; Jonathan M. Schott
• Keywords: Concordance; Amyloid (mycology); Standardized uptake value

Alzheimer's disease has a preclinical stage when cerebral amyloid-b deposition occurs before symptoms emerge, and amyloid-b-targeted therapies may have maximum benefits.Existing status measurement techniques, including amyloid PET CSF testing, are difficult to deploy at scale, so blood biomarkers increasingly considered for screening.We compared three different blood-based techniques-liquid chromatography-mass spectrometry measures of plasma amyloid-b, single molecule array (Simoa) phospho-tau181-to detect cortical 18 F-florbetapir positivity (defined as standardized uptake value ratio 40.61 between predefined region interest eroded subcortical white matter) in dementia-free members Insight 46, substudy the population-based British 1946 birth cohort.We used logistic regression models with predictors status, or without age, sex APOE e4 carrier covariates.We generated receiver operating characteristics curves quantified areas under compare concordance tests PET.We determined test cut-off points using Youden's index, then estimated numbers needed screen obtain 100 PET-positive individuals.Of 502 individuals assessed, 441 complete data were included; 82 (18.6%) PET-positive.The area curve base model comprising was 0.695 (95% confidence interval: 0.628-0.762).The two best-performing Simoa 42/40 (0.620; 0.548-0.691)and phospho-tau181 (0.707; 0.646-0.768),but neither outperformed model.Mass performed significantly better than any other measure (amyloid-b 1-42/1-40 : 0.817; 0.770-0.864and composite: 0.820; 0.775-0.866).At point 0.095, mass detected 86.6% sensitivity 71.9% specificity.Without screening, from population similar prevalence 543 scans would need be performed.Screening require 940 individuals, whom 266 proceed scan.Using alone reduce these 623 243 respectively.Across theoretical range 10-50%, consistently proceeding scans, greater cost savings demonstrated lower prevalence.