Association between transthyretin levels and Alzheimer's disease: A meta-analysis

Transthyretin (TTR) has been implicated in amyloid-β (Aβ) binding, cerebrospinal fluid homeostasis, and neurodegenerative processes in Alzheimer's disease (AD), but clinical evidence regarding its levels in AD and mild cognitive impairment (MCI) remains inconsistent.

This meta-analysis aimed to clarify the association between blood/cerebrospinal fluid (CSF) TTR levels and AD/MCI.

Following the PRISMA guidelines, this meta-analysis systematically identified and included 18 eligible studies from databases including PubMed, Web of Science, Embase, and Cochrane Library.

Random-effects meta-analysis showed lower TTR levels in AD versus healthy controls (HC) (Hedges' g = -0.77, 95% CI: -1.50, -0.04; p = 0.04), with no significant differences in MCI versus HC. Subgroup analyses confirmed a significant reduction in TTR levels across multiple dimensions: 1) sample types (serum); 2) population characteristics (age difference < 5 years and sex difference ≥ 10%); and 3) detection methods (immunoassay). Multivariate meta-regression with region, sample source, detection technology, and female ratio difference as covariates, accounted for 36.81% of the between-study heterogeneity. Sensitivity analysis verified result robustness, and publication bias was resolved after excluding an outlier study.

Lower TTR levels are significantly associated with AD. This finding suggests that TTR warrants further investigation as a candidate biomarker for AD, although prospective studies are needed to validate its clinical utility.