Serum Tau-A and Tau-C Levels and Their Association with Cognitive Impairment and Dementia Progression in a Memory Clinic Derived Cohort
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Serum-measured fragments of Tau cleaved by ADAM-10 (Tau-A) and Caspase-3 (Tau-C) have been found linked to change in cognitive function and risk of dementia.
Objectives
1) To determine the discriminatory abilities of Tau-A, and Tau-C in subjects with either mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) or AD dementia compared to a control group. 2) To determine if there is a relation between Tau-A, and Tau-C and established cerebrospinal fluid (CSF) markers of AD- β-Amyloid1-42 (AB42), Phosphorylated-tau-181 (p-tau), and total-tau. 3) To determine if Tau-A and Tau-C are associated with progression rate from MCI due to AD to AD dementia.
Design
Cross-sectional and a substudy using a retrospective cohort design.
Setting
Memory clinic derived subjects contributing to the Danish Dementia Biobank.
Participants
Cognitively unimpaired subjects (n=49), patients with mild cognitive impairment (MCI) due to AD (n=45), and Alzheimer’s dementia (n=52).
Measurements
Competitive enzyme-linked immunosorbent assay (ELISA)-measured serum levels of Tau-A, and Tau-C.
Results
The ratio between Tau-A and Tau-C differed between the three groups (p=0.015). Age- and sex-adjusted Tau-A differed between groups with lower ratios being associated with more severe disease (p=0.023). Tau-C was trending towards significant correlation to CSF-levels of AB42 (Pearson correlation coefficient 0.164, p=0.051). Those with Tau-C-levels in the 2nd quartile had a hazard ratio (HR) of 2.91 (95% CI 1.01–8.44, p=0.04) of progression compared to those in the 1st quartile. Those in the 3rd quartile was found to have a borderline significant (p=0.055) HR of 2.63 (95% CI 0.98–7.05) when compared to those in the lowest quartile.
Conclusions
Tau-A and the ratio between Tau-A and Tau-C showed significant differences between groups and were correlated to CSF-AB42. Tau-C values in the middle range were associated with faster progression from MCI to dementia. This pilot study adds to the mounting data suggesting serum-measured Tau-A and Tau-C as biomarkers useful in relation to diagnosis and progression rate in AD but need further validation.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Prevention of Alzheimer's Disease |
| Antal sider | 9 |
| ISSN | 2274-5807 |
| DOI | |
| Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:
Funding: The project has been initiated by the principal investigator Tobias Melton Axelsen in collaboration with Nordic Bioscience A/S. The project is partly funded by Nordic Bioscience covered the costs of the measurements of the Tau-fragments. Tobias M. Axelsen is funded by a grant from the Danish Research Fund. The fee for obtaining the samples from the Danish Dementia Biobank was provided by Sanos Group A/S. This fee ensures payment of staff for the handling of samples, selection of relevant patients and data as well as scientific involvement in the study. The Danish Dementia Biobank is partially funded by the Absalon Foundation and Toyota Fonden Denmark.
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