Association of thyroid autoimmune status with Alzheimer's disease biomarkers in euthyroid subjects

The link between thyroid autoimmunity and Alzheimer's disease (AD) biomarkers in euthyroid individuals is poorly understood. We investigated the independent and interactive effects of thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) on core cerebrospinal fluid (CSF) biomarkers of AD pathology.

We analyzed CSF biomarkers (Aβ1-42, Aβ1-40, T-tau, and P-tau181) measured using validated ELISA assays (Fujirebio) in 114 euthyroid, amyloid-positive participants stratified by antibody status. Associations were assessed using multiple linear regression and four-group cross-classification analyses, adjusting for age and gender.

TPOAb positivity was independently associated with a significantly lower CSF Aβ1-42/Aβ1-40 ratio (mean ± SD: 0.04 ± 0.01 vs. 0.05 ± 0.02; adjusted p=0.022; Cohen's d = -0.65), indicating more advanced amyloid pathology. Importantly, we identified a novel interaction modulating tau pathology: isolated positivity for either TPOAb or TgAb was linked to elevated P-tau181, but this effect was significantly attenuated in subjects positive for both antibodies (interaction p=0.037).

Thyroid autoimmunity is associated with AD neuropathological changes independent of thyroid hormone status. The specific association of TPOAb with amyloid pathology and the complex interplay between antibodies on tau pathology highlight previously unrecognized mechanisms. These findings, pending validation in longitudinal studies, suggest thyroid antibody screening in elderly euthyroid individuals may aid in identifying those at higher risk for Alzheimer's pathology, potentially facilitating earlier detection and intervention.