Gene Association Study of the Urokinase Plasminogen Activator and Its Receptor Gene in Alzheimer’s Disease

Article type: Research Article

Authors: Cetinsoy, Ozde^a | Anyanwu, Ijeoma^a | Krishnanand, Harikrishnan^a | Natarajan, Gokulakrishnan^a | Ramachandran, Naveen^a | Thomas, Alan^b | Brookes, Keeley J.^{a; *}

Affiliations: [a] Biosciences, Clifton Campus, Nottingham Trent University, Nottingham, UK | [b] Brains for Dementia Research, Faculty of Medical Sciences, Newcastle University, Newcastle, UK

Correspondence: [*] Correspondence to: Keeley Brookes, Biosciences, Clifton Campus, Nottingham Trent University, Nottingham, UK. E-mail: [email protected].

Abstract: Background:The role of the innate immune system has long been associated with Alzheimer’s disease (AD). There is now accumulating evidence that the soluble Urokinase Plasminogen Activator Receptor pathway, and its genes, PLAU and PLAUR may be important in AD, and yet there have been few genetic association studies to explore this. Objective:This study utilizes the DNA bank of the Brains for Dementia Research cohort to investigate the genetic association of common polymorphisms across the PLAU and PLAUR genes with AD. Methods:TaqMan genotyping assays were used with standard procedures followed by association analysis in PLINK. Results:No association was observed between the PLAU gene and AD; however, two SNPs located in the PLAUR gene were indicative of a trend towards association but did not surpass multiple testing significance thresholds. Conclusions:Further genotyping studies and exploration of the consequences of these SNPs on gene expression and alternative splicing are warranted to fully uncover the role this system may have in AD.

Keywords: Alzheimer’s disease, association, BDR, innate immune system, PLAUR , PLAU , suPAR

DOI: 10.3233/JAD-231383

Journal: Journal of Alzheimer's Disease, vol. 99, no. 1, pp. 241-250, 2024