Lack of association between bridging integrator 1 () rs744373 polymorphism and tau-PET load in cognitively intact older adults.

Introduction: The bridging integrator 1( rs744373 risk polymorphism has been linked to increased [F]AV1451 signal in non-demented older adults (ie., mild cognitive impairment [MCI] plus cognitively normal [CN] individuals). However, the association of with in vivo tau, amyloid beta (Aβ) burden, and cognitive impairment in the asymptomatic stage of Alzheimer's disease (AD) remains unknown.

Methods: The effect on [F]AV1451 binding was evaluated in 59 cognitively normal (CN) participants (39% apolipoprotein E [ ε4]) from the Flemish Prevent AD Cohort KU Leuven (F-PACK), as well as in 66 Alzheimer's Disease Neuroimaging Initiative (ADNI) CN participants, using voxelwise and regional statistics. For comparison, 52 MCI patients from ADNI were also studied.

Results: Forty-four percent of F-PACK participants were rs744373 risk-allele carriers, 21% showed high amyloid burden, and 8% had elevated [F]AV1451 binding. In ADNI, 53% and 50% of CNs and MCIs, respectively, carried the rs744373 risk-allele. Amyloid positivity was present in 23% of CNs and 51% of MCIs, whereas 2% of CNs and 35% of MCIs showed elevated [F]AV1451 binding. There was no significant effect of on voxelwise or regional [F]AV1451 in F-PACK or ADNI CNs, or in the pooled CN sample. No significant association between and [F]AV1451 was obtained in ADNI MCI patients. However, in the MCI group, numerically higher [F]AV1451 binding was observed in the risk-allele group compared to the normal group in regions corresponding to more progressed tau pathology.

Discussion: We could not confirm the association between rs744373 risk-allele and elevated [F]AV1451 signal in CN older adults or MCI. Numerically higher [F]AV1451 binding was observed, however, in the MCI risk-allele group, indicating that the previously reported positive effect may be confounded by group. Therefore, when studying how the risk polymorphism influences AD pathogenesis, a distinction should be made between asymptomatic, MCI, and dementia stages of AD.