Plasma phospho-tau181 in presymptomatic and symptomatic familial Alzheimer's disease: a longitudinal cohort study

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 cha...

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Published in:	Molecular psychiatry 2021-10, Vol.26 (10), p.5967-5976
Main Authors:	O'Connor, Antoinette, Karikari, Thomas K, Poole, Teresa, Ashton, Nicholas J, Lantero Rodriguez, Juan, Khatun, Ayesha, Swift, Imogen, Heslegrave, Amanda J, Abel, Emily, Chung, Elisha, Weston, Philip S J, Pavisic, Ivanna M, Ryan, Natalie S, Barker, Suzie, Rossor, Martin N, Polke, James M, Frost, Chris, Mead, Simon, Blennow, Kaj, Zetterberg, Henrik, Fox, Nick C
Format:	Article
Language:	eng
Subjects:	Alzheimer Disease - genetics Alzheimer's disease Alzheimers disease Biochemistry & Molecular Biology Biomarkers Clinical trials Cohort analysis Cohort Studies Development and progression Diagnosis Health aspects Humans Longitudinal Studies Mutation Neurodegenerative diseases Neurosciences Neurosciences & Neurology Neurovetenskaper Physiological aspects Plasma Psychiatry tau Tau proteins tau Proteins - genetics
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Summary:	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
ISSN:	1359-4184 1476-5578