Serum Tau-A and Tau-C Levels and Their Association with Cognitive Impairment and Dementia Progression in a Memory Clinic Derived Cohort - 21/11/24
, P. Høgh 4, 7, A.R. Bihlet 5, M.A. Karsdal 3, K. Henriksen 3, S.G. Hasselbalch 6, 7, A.H. Simonsen 6
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Abstract |
Background |
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.
Le texte complet de cet article est disponible en PDF.Key words : Serum biomarkers, Alzheimer’s disease, progression rate, tau-A, tau-C, tau-fragments
Plan
Vol 11 - N° 3
P. 730-738 - mai 2024 Retour au numéro
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