Dataset Information
Lack of association between bridging integrator 1 (BIN1) rs744373 polymorphism and tau-PET load in cognitively intact older adults.
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ABSTRACT: Introduction
The bridging integrator 1(BIN1) rs744373 risk polymorphism has been linked to increased [18F]AV1451 signal in non-demented older adults (ie., mild cognitive impairment [MCI] plus cognitively normal [CN] individuals). However, the association of BIN1 with in vivo tau, amyloid beta (Aβ) burden, and cognitive impairment in the asymptomatic stage of Alzheimer's disease (AD) remains unknown.Methods
The BIN1 effect on [18F]AV1451 binding was evaluated in 59 cognitively normal (CN) participants (39% apolipoprotein E [APOE 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 BIN1 rs744373 risk-allele carriers, 21% showed high amyloid burden, and 8% had elevated [18F]AV1451 binding. In ADNI, 53% and 50% of CNs and MCIs, respectively, carried the BIN1 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 [18F]AV1451 binding. There was no significant effect of BIN1 on voxelwise or regional [18F]AV1451 in F-PACK or ADNI CNs, or in the pooled CN sample. No significant association between BIN1 and [18F]AV1451 was obtained in ADNI MCI patients. However, in the MCI group, numerically higher [18F]AV1451 binding was observed in the BIN1 risk-allele group compared to the BIN1 normal group in regions corresponding to more progressed tau pathology.Discussion
We could not confirm the association between BIN1 rs744373 risk-allele and elevated [18F]AV1451 signal in CN older adults or MCI. Numerically higher [18F]AV1451 binding was observed, however, in the MCI BIN1 risk-allele group, indicating that the previously reported positive effect may be confounded by group. Therefore, when studying how the BIN1 risk polymorphism influences AD pathogenesis, a distinction should be made between asymptomatic, MCI, and dementia stages of AD.
SUBMITTER: Schaeverbeke J
PROVIDER: S-EPMC8864573 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Publications
Lack of association between bridging integrator 1 (<i>BIN1</i>) rs744373 polymorphism and tau-PET load in cognitively intact older adults.
Alzheimer's & dementia (New York, N. Y.) 20220223 1
<h4>Introduction</h4>The bridging integrator 1(<i>BIN1)</i> rs744373 risk polymorphism has been linked to increased [<sup>18</sup>F]AV1451 signal in non-demented older adults (ie., mild cognitive impairment [MCI] plus cognitively normal [CN] individuals). However, the association of <i>BIN1</i> with in vivo tau, amyloid beta (Aβ) burden, and cognitive impairment in the asymptomatic stage of Alzheimer's disease (AD) remains unknown.<h4>Methods</h4>The <i>BIN1</i> effect on [<sup>18</sup>F]AV1451 ...[more]