A genetic signature including apolipoprotein Eε4 potentiates the risk of herpes simplex–associated Alzheimer's disease

• Published in: Alzheimer's & Dementia: Translational Research & Clinical Interventions
• Main Authors: Lopatko Lindman, Karin, Weidung, Bodil, Olsson, Jan, Josefsson, Maria, Kok, Eloise, Johansson, Anders, Eriksson, Sture, Hallmans, Göran, Elgh, Fredrik, Lövheim, Hugo
• Other Authors: European Commission, Västerbotten Läns Landsting, Knut och Alice Wallenbergs Stiftelse, Umeå Universitet, Kempestiftelserna, Sveriges Läkarförbund
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2019
• Subjects: Iceland
• Online Access: http://dx.doi.org/10.1016/j.trci.2019.09.014; https://api.elsevier.com/content/article/PII:S2352873719300757?httpAccept=text/xml; https://api.elsevier.com/content/article/PII:S2352873719300757?httpAccept=text/plain; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1016%2Fj.trci.2019.09.014; https://onlinelibrary.wiley.com/doi/pdf/10.1016/j.trci.2019.09.014; https://onlinelibrary.wiley.com/doi/full-xml/10.1016/j.trci.2019.09.014

Abstract Introduction Herpes simplex virus type 1 (HSV1) in combination with genetic susceptibility has previously been implicated in Alzheimer's disease (AD) pathogenesis. Methods Plasma from 360 AD cases, obtained on average 9.6 years before diagnosis, and their age‐ and sex‐matched controls, were analyzed for anti–HSV1 immunoglobulin (Ig) G with enzyme‐linked immunosorbent assays (ELISAs). A POE genotype and nine other selected risk genes for AD were extracted from a genome‐wide association study analysis by deCODE genetics, Reykjavik, Iceland. Results The interaction between APOEε 4 heterozygosity ( APOEε 2 /ε 4 or ε 3/ ε 4) and anti–HSV1 IgG carriage increased the risk of AD (OR 4.55, P = .02). A genetic risk score based on the nine AD risk genes also interacted with anti–HSV1 IgG for the risk of developing AD (OR 2.35, P = .01). Discussion The present findings suggest that the APOEε 4 allele and other AD genetic risk factors might potentiate the risk of HSV1‐associated AD.