Serum transthyretin (TTR) may be an early biomarker for Alzheimer's disease and related
disorders (ADRD). We investigated associations of TTR measured at baseline with cognitive
decline and incident ADRD and whether TTR trajectories differ between ADRD cases and
non-cases, over 22 years before diagnosis. A total of 6024 adults aged 45-69 in 1997-1999
were followed up until 2019. TTR was assessed three times, and 297 cases of dementia
were recorded. Higher TTR was associated with higher cognitive function at baseline;
however, TTR was unrelated to subsequent change in cognitive function. TTR at baseline
did not predict ADRD risk (hazard ratio per SD TTR (4.8 mg/dL) = 0.97; 95% confidence
interval: 0.94-1.00). Among those later diagnosed with ADRD, there was a marginally
steeper downward TTR trajectory than those free of ADRD over follow-up (P=0.050).
Our findings suggest TTR is not neuroprotective. The relative decline in TTR level
in the preclinical stage of ADRD is likely to be a consequence of disease processes.
