Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Apr 29:14:889101.
doi: 10.3389/fnagi.2022.889101. eCollection 2022.

Plasma Phosphorylated-tau181 Is a Predictor of Post-stroke Cognitive Impairment: A Longitudinal Study

Li-Kai Huang  1   2   3   4   5 , Shu-Ping Chao  1   2   4 , Chaur-Jong Hu  1   2   4   6   7 , Li-Nien Chien  8   9   10 , Hung-Yi Chiou  11   12   13 , Yu-Chun Lo  7 , Yi-Chen Hsieh  7   12   14
Affiliations

Plasma Phosphorylated-tau181 Is a Predictor of Post-stroke Cognitive Impairment: A Longitudinal Study

Li-Kai Huang et al. Front Aging Neurosci. .

Abstract

Introduction: Post-stroke cognitive impairment (PSCI) cannot be neglected because it drastically influences the daily life of patients and their families. However, there are no studies exploring the association between preclinical blood biomarkers of neurodegeneration including plasma amyloid-β (Aβ), tau, and brain-derived neurotrophic factor (BDNF) together with the risk of PSCI. This longitudinal study was to investigate whether these blood biomarkers with imaging markers of cerebral small vessel disease can improve the prediction for PSCI. In addition, we also explored the association between blood biomarkers with the trajectories of PSCI.

Methods: Adult patients with first-ever acute ischemic stroke were recruited, and the cognitive and functional abilities of these patients were evaluated. Furthermore, blood biomarkers of neurodegeneration including plasma Aβ-40, Aβ-42, total tau, phosphorylated tau 181 (p-tau181), and BDNF levels and image markers of cerebral small vessel disease were measured. Each patient was followed up at 3 and 12 months at the outpatient department.

Results: Of 136 patients, 40 and 50 patients developed PSCI at 3 and 12 months after stroke, respectively. In functional trajectories, 27 patients did not have PSCI at 3 months but did at 12 months. By contrast, the PSCI status of 17 patients at 3 months was reversed at 12 months. Patients with high-acute plasma p-tau181 had a significantly lower PSCI risk at 3 months (odds ratio [OR] = 0.62, 95% CI = 0.40-0.94, p = 0.0243) and 12 months (OR = 0.69, 95% CI = 0.47-0.99, p = 0.0443) after adjustment for covariates and image biomarkers. Discrimination and reclassification statistics indicated that the p-tau181 level can improve discrimination ability for PSCI at 3 and 12 months, respectively. In addition, the plasma p-tau181 level was the highest in subjects without PSCI followed by those with delayed-onset PSCI and early-onset PSCI with reversal, whereas the lowest plasma p-tau181 level was found among those with persistent PSCI, showing a significant trend test (p = 0.0081).

Conclusion: Plasma p-tau181 is a potential biomarker for predicting early- and delayed-onset PSCI. Future studies should incorporate plasma p-tau181 as an indicator for timely cognitive intervention in the follow-up of patients with stroke.

Keywords: biomarker; delayed-onset PSCI; early-onset PSCI; ischemic stroke; p-tau181.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flowchart of patient enrollment and cognitive function changes during the 12 months’ follow-up.
FIGURE 2
FIGURE 2
The area under the receiver operating characteristic of the p-tau181 predicting PSCI at 3 (A) and 12 months (B), respectively, when compared to conventional risk factors with image markers.
See this image and copyright information in PMC

References

    1. Abzhandadze T., Rafsten L., Lundgren Nilsson ÅC., Palstam A., Sunnerhagen K. S. (2019). Very early MoCA can predict functional dependence at 3 months after stroke: a longitudinal, cohort study. Front. Neurol. 10:1051. 10.3389/fneur.2019.01051 - DOI - PMC - PubMed
    1. Adams H. P., Davis P., Leira E., Chang K.-C., Bendixen B., Clarke W., et al. (1999). Baseline NIH Stroke Scale score strongly predicts outcome after stroke: a report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology 53 126–131. 10.1212/wnl.53.1.126 - DOI - PubMed
    1. Albert M. S., DeKosky S. T., Dickson D., Dubois B., Feldman H. H., Fox N. C., et al. (2011). The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 7 270–279. 10.1016/j.jalz.2011.03.008 - DOI - PMC - PubMed
    1. Alonso A. C., Li B., Grundke-Iqbal I., Iqbal K. (2006). Polymerization of hyperphosphorylated tau into filaments eliminates its inhibitory activity. Proc. Natl. Acad. Sci. U.S.A. 103 8864–8869. 10.1073/pnas.0603214103 - DOI - PMC - PubMed
    1. Alonso A. C., Zaidi T., Novak M., Grundke-Iqbal I., Iqbal K. (2001). Hyperphosphorylation induces self-assembly of τ into tangles of paired helical filaments/straight filaments. Proc. Natl. Acad. Sci. U.S.A. 98 6923–6928. 10.1073/pnas.121119298 - DOI - PMC - PubMed