Serum tyrosine associates with increased CSF Aβ42, reduced Aβ deposition, and cognitive improvement in MCI: modulation by confounding factors.

Tyrosine, a precursor to dopamine, norepinephrine, and epinephrine, has shown mixed results in cognitive impairment studies, suggesting a complex role in mild cognitive impairment (MCI). This study is the first to explore its relationship with CSF amyloid-beta (Aβ) 42, Aβ accumulation, and cognitive function in MCI (n = 251). Cognitive function was assessed using ADAS-Cog, serum tyrosine by UPLC-MS/MS, Aβ42 by ELISA, and Aβ accumulation via florbetapir PET with SUVr, all validated with quality control. Two analysis models were used: Model 1 (unadjusted) and Model 2 (adjusted for age, gender, education, handedness, and ApoE status). The study found a significant positive link between serum tyrosine levels and CSF Aβ42, with higher tyrosine levels associated with increased Aβ42, independent of demographic and genetic factors. Mediation analysis revealed that in Model 1, higher serum tyrosine was associated with improved cognitive function, potentially through increased CSF Aβ42 levels. However, this association was not present after adjusting for confounders in Model 2. Further investigation of Aβ accumulation in specific brain regions (global, frontal, temporal, and parietal lobes) found that, in Model 1, higher serum tyrosine was linked to reduced Aβ accumulation in the frontal and temporal lobes, wich in turn correlated with better cognitive function. Yet, after adjusting for confounders in Model 2, these effects were no longer significant. Overall, the findings suggest that while serum tyrosine may influence cognitive improvement in MCI through its relationship with CSF Aβ42 and Aβ accumulation, these effects are strongly influenced by demographic and genetic factors.