Lack of Association Between Bridging Integrator 1 () Rs744373 Polymorphism and Tau-PET Load in Cognitively Intact Older Adults

Overview

Journal Alzheimers Dement (N Y)

Date 2022 Mar 1

PMID 35229019

Authors

Jolien Schaeverbeke

Emma S Luckett

Silvy Gabel

Mariska Reinartz

Steffi De Meyer

Isabelle Cleynen

Kristel Sleegers

Christine Van Broeckhoven

Guy Bormans

Kim Serdons

Koen Van Laere

Patrick Dupont

Rik Vandenberghe

Affiliations

Soon will be listed here.

Abstract

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.

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

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