- April 17, 2026
- David J Hunter, et al., University of Oxford
Topic/Product:
CNS Disease Panel 120
Disease Area:
Alzheimer's Disease
Sample Type:
Plasma
Abstract
Identifying individuals in the preclinical stages of Alzheimer’s disease (AD) is necessary for inclusion into future prevention trials. AD pathology occurs in the brain 20 or more years before diagnosis. In a nested 1:1 matched case-control sample of 426 participants selected from 19,500 members of the EPIC-Oxford cohort, we found that higher blood-based brain-derived and total p-tau 181, 217, and 231, as well as GFAP, were associated with AD over up to 25 years of follow-up (median=19.4, interquartile range 16.8-21.9 years). Of these seven biomarkers, LASSO regression selected brain-derived p-tau 217 as the strongest discriminator of AD cases from controls. The AUC for brain-derived p-tau 217 accounting for age, sex, and time of blood draw was 0.80, which increased to 0.82, 0.83, 0.84, after further addition of 1) APOE-e4 carrier status, 2) sociodemographic and lifestyle factors, and 3) both, respectively. Blood-based biomarkers, including the novel brain-derived p-tau 217, could identify individuals at-risk of AD two decades pre-diagnosis.Identifying individuals in the preclinical stages of Alzheimer’s disease (AD) is necessary for inclusion into future prevention trials. AD pathology occurs in the brain 20 or more years before diagnosis. In a nested 1:1 matched case-control sample of 426 participants selected from 19,500 members of the EPIC-Oxford cohort, we found that higher blood-based brain-derived and total p-tau 181, 217, and 231, as well as GFAP, were associated with AD over up to 25 years of follow-up (median=19.4, interquartile range 16.8-21.9 years). Of these seven biomarkers, LASSO regression selected brain-derived p-tau 217 as the strongest discriminator of AD cases from controls. The AUC for brain-derived p-tau 217 accounting for age, sex, and time of blood draw was 0.80, which increased to 0.82, 0.83, 0.84, after further addition of 1) APOE-e4 carrier status, 2) sociodemographic and lifestyle factors, and 3) both, respectively. Blood-based biomarkers, including the novel brain-derived p-tau 217, could identify individuals at-risk of AD two decades pre-diagnosis.
Authors & Affiliations
Thomas J. Littlejohns¹, Wenyu Liu¹, Christopher Maronga², Tammy Y.N. Tong², Najaf Amin¹, Marie Breeur², Jennifer Collister¹, Mahboubeh Parsaeian², Keren Papier², Paolo Piazza³, Gabrielle Rockett³, Karl Smith-Byrne², Ruth C. Travis², Cornelia M. van Duijn¹, and David J. Hunter¹⁴
¹ Nuffield Department of Population Health, University of Oxford, Oxford, UK
² Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
³ Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK
⁴ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA