Plasma phospho-tau181 in presymptomatic and symptomatic familial Alzheimer’s disease: a longitudinal cohort study
Open accessAbstract
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.
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This relationship is observed across the AD continuum, including the asymptomatic phase in sporadic and genetic forms of AD.
“This relationship is observed across the AD continuum, including the asymptomatic phase in sporadic and genetic forms of AD.11,12,13,14”
From Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology (2024) · cites this paper as [11]
The Discussion (page not provided) reports elevated plasma p-tau181 in both presymptomatic and symptomatic familial AD mutation carriers. It also describes reports of elevated blood p-tau181 in cognitively normal amyloid-positive individuals and in sporadic AD dementia. The paper therefore supports observations at those stages, but its own cohort studied familial AD, not the relationship across the full sporadic AD continuum. (LLM, conf=0.82)
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- Authors
- O’Connor, A., Karikari, T. K., Poole, T., Ashton, N. J., Lantero Rodriguez, J., Khatun, A., Swift, I., Heslegrave, A. J., Abel, E., Chung, E., Weston, P. S. J., Pavisic, I. M., Ryan, N. S., Barker, S., Rossor, M. N., Polke, J. M., Frost, C., Mead, S., Blennow, K., Zetterberg, H., & Fox, N. C.
- Affiliations
- UK Dementia Research Institute (GB)
- University of Gothenburg (SE)
- London School of Hygiene & Tropical Medicine (GB)
- King's College London (GB)
- UCL Queen Square Institute of Neurology (GB)
- University College London Hospitals NHS Foundation Trust (GB)
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Zetterberg, Henrik
- Fox, Nick C.
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2020-07-14
- Volume
- 26
- Issue
- 10
- Pages
- 5967-5976
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC7612227
- OpenAlex
- W3043470682
- Cited by
- 122
- References
- 47
- Citations by year
- 2026: 12 · 2025: 11 · 2024: 16 · 2023: 19 · 2022: 33 · 2021: 28 · 2020: 3
- FWCI
- 12.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Alzheimer's Society
- National Institute for Health and Care Research (NF-SI-0617-10175)
- Rosetrees Trust (M668-CD1)
- Medical Research Council (MR/L023784/2, MR/M003108/1, MR/L023784/1)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- familial Alzheimer's disease, preclinical Alzheimer's disease, blood biomarkers, neurofilament light chain, mutation carriers, clinical severity, early detection of Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Humans, Longitudinal Studies, Cohort Studies, Biomarkers, tau Proteins
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