TY  - INPR
KW  - Diagnostic markers
KW  -  Predictive markers
ID  - discovery10107467
A1  - O'Connor, A
A1  - Karikari, TK
A1  - Poole, T
A1  - Ashton, NJ
A1  - Rodriguez, JL
A1  - Khatun, A
A1  - Swift, I
A1  - Heslegrave, AJ
A1  - Abel, E
A1  - Chung, E
A1  - Weston, PSJ
A1  - Pavisic, IM
A1  - Ryan, NS
A1  - Barker, S
A1  - Rossor, MN
A1  - Polke, JM
A1  - Frost, C
A1  - Mead, S
A1  - Blennow, K
A1  - Zetterberg, H
A1  - Fox, NC
UR  - https://doi.org/10.1038/s41380-020-0838-x
N2  - Blood biomarkers have great potential to advance clinical care and accelerate trials in Alzheimer?s disease (AD). Plasma phospho-tau181 (p-tau181) is a promising blood biomarker however, it is unknown if levels increase in presymptomatic AD. Therefore, we investigated the timing of p-tau181 changes using 153 blood samples from 70 individuals in a longitudinal study of familial AD (FAD). Plasma p-tau181 was measured, using an in-house single molecule array assay. We compared p-tau181 between symptomatic carriers, presymptomatic carriers, and non-carriers, adjusting for age and sex. We examined the relationship between p-tau181 and neurofilament light and estimated years to/from symptom onset (EYO), as well as years to/from actual onset in a symptomatic subgroup. In addition, we studied associations between p-tau181 and clinical severity, as well testing for differences between genetic subgroups. Twenty-four were presymptomatic carriers (mean baseline EYO ?9.6 years) while 27 were non-carriers. Compared with non-carriers, plasma p-tau181 concentration was higher in both symptomatic (p?<?0.001) and presymptomatic mutation carriers (p?<?0.001). Plasma p-tau181 showed considerable intra-individual variability but individual values discriminated symptomatic (AUC 0.93 [95% CI 0.85?0.98]) and presymptomatic (EYO????7 years) (AUC 0.86 [95% CI 0.72?0.94]) carriers from non-carriers of the same age and sex. From a fitted model there was evidence (p?=?0.050) that p-tau181 concentrations were higher in mutation carriers than non-carriers from 16 years prior to estimated symptom onset. Our finding that plasma p-tau181 concentration is increased in symptomatic and presymptomatic FAD suggests potential utility as an easily accessible biomarker of AD pathology.
AV  - public
JF  - Molecular Psychiatry
EP  - 10
TI  - Plasma phospho-tau181 in presymptomatic and symptomatic familial Alzheimer's disease: a longitudinal cohort study
Y1  - 2020/07/14/
PB  - NATURE PUBLISHING GROUP
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
ER  -