Skipping of FCER1G Exon 2 Is Common in Human Brain But Not Associated with the Alzheimer's Disease Genetic Risk Factor rs2070902

Alyssa C Feldner; Andrew K Turner; James F Simpson; Steven Estus

doi:10.3233/ADR-230076

Skipping of FCER1G Exon 2 Is Common in Human Brain But Not Associated with the Alzheimer's Disease Genetic Risk Factor rs2070902

J Alzheimers Dis Rep. 2023 Nov 30;7(1):1313-1322. doi: 10.3233/ADR-230076. eCollection 2023.

Authors

Alyssa C Feldner¹, Andrew K Turner¹, James F Simpson¹, Steven Estus¹

Affiliation

¹ Department of Physiology and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.

Abstract

Background: Understanding the mechanisms whereby genetic variants influence the risk of Alzheimer's disease (AD) may provide insights into treatments that could reduce AD risk.

Objective: Here, we sought to test the hypothesis that a single nucleotide polymorphism (SNP) associated with AD risk, rs2070902, influences splicing of FCER1G exon 2.

Methods: AD and non-AD brain samples were analyzed for FCER1G expression by genotyping, immunohistochemistry, immunofluorescence, and qPCR.

Results: The protein encoded by FCER1G, FcRγ, is robustly expressed in microglia in both AD and non-AD brain. The FCER1G isoform lacking exon 2 (D2-FCER1G) was readily detectable. Moreover, the proportion of FCER1G expressed as this isoform was increased in brains with high AD neuropathology. However, the proportion of FCER1G expressed as the D2-FCER1G isoform was not associated with rs2070902 genotype.

Conclusions: In summary, the proportion of FCER1G expressed as the D2-FCER1G isoform is increased with AD neuropathology but is not associated with rs2070902.

Keywords: Alzheimer’s disease; RNA splicing; genetics; microglia; polymorphism.

Abstract

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