Longitudinal change in CSF Tau and Aβ biomarkers for up to 48 months in ADNI
Open accessAbstract
The dynamics of cerebrospinal fluid (CSF) tau and Aβ biomarkers over time in Alzheimer's disease (AD) patients from prodromal pre-symptomatic to severe stages of dementia have not been clearly defined and recent studies, most of which are cross-sectional, present conflicting findings. To clarify this issue, we analyzed the longitudinal CSF tau and Aβ biomarker data from 142 of the AD Neuroimaging Initiative (ADNI) study subjects [18 AD, 74 mild cognitive impairment (MCI), and 50 cognitively normal subjects (CN)]. Yearly follow-up CSF collections and studies were conducted for up to 48 months (median = 36 months) for CSF Aβ1-42, phosphorylated tau (p-tau181), and total tau (t-tau). An unsupervised analysis of longitudinal measurements revealed that for Aβ1-42 and p-tau181 biomarkers there was a group of subjects with stable longitudinal CSF biomarkers measures and a group of subjects who showed a decrease (Aβ1-42, mean = -9.2 pg/ml/year) or increase (p-tau181, mean = 5.1 pg/ml/year) of these biomarker values. Low baseline Aβ1-42 values were associated with longitudinal increases in p-tau181. Conversely, high baseline p-tau181 values were not associated with changes in Aβ1-42 levels. When the subjects with normal baseline biomarkers and stable concentrations during follow-up were excluded, the expected time to reach abnormal CSF levels and the mean AD values was significantly shortened. Thus, our data demonstrate for the first time that there are distinct populations of ADNI subjects with abnormal longitudinal changes in CSF p-tau181 and Aβ1-42 levels, and our longitudinal results favor the hypothesis that Aβ1-42 changes precede p-tau181 changes.
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CSF p-tau biomarkers likely indicate an active process of tau secretion, and one that is correlated with cerebral Aβ deposition in early disease.
“Thus, it is suggested that CSF p-tau biomarkers likely indicate an active process of tau secretion, and one that is correlated with cerebral Aβ deposition in early disease.20, 21, 22”
From Cerebrospinal fluid p-tau231 as an early indicator of emerging pathology in Alzheimer's disease (2022) · cites this paper as [21]
The Results and Discussion (page unavailable) report that low baseline CSF Aβ1–42 was associated with subsequent increases in CSF p-tau181, supporting a relationship between the biomarkers in the studied cohort. They do not establish that p-tau indicates active tau secretion or directly show a correlation with cerebral Aβ deposition; the association measured here was with CSF Aβ1–42. (LLM, conf=0.86)
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- Authors
- Toledo, J. B., Xie, S. X., Trojanowski, J. Q., & Shaw, L. M.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Shaw, Leslie M.
- Venue
- Acta Neuropathologica
- Published
- 2013-06-29
- Volume
- 126
- Issue
- 5
- Pages
- 659-670
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC3875373
- OpenAlex
- W2025983435
- Cited by
- 180
- References
- 9
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 7 · 2023: 4 · 2022: 14 · 2021: 22 · 2020: 25 · 2019: 12 · 2018: 12 · 2017: 18 · 2016: 14 · 2015: 19 · 2014: 19 · 2013: 3
- FWCI
- 13.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Mayo Clinic
- University of Pennsylvania
- National Institutes of Health (5u01ag024904-10)
- National Institute on Aging (U01-AG-024904, P30AG010129, K01AG030514, P30AG010124, AG-10124, AG24904, U19AG024904)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- Alzheimer's disease, cerebrospinal fluid biomarkers, tau protein, amyloid-beta, amyloid-beta 42, phosphorylated tau 181, total tau, longitudinal biomarker changes, mild cognitive impairment, prodromal Alzheimer's disease, disease progression, ADNI
- MeSH terms
- Aged, Alzheimer Disease, Female, Humans, Immunoassay, Longitudinal Studies, Male, Biomarkers, Amyloid beta-Peptides, tau Proteins
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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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