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

Karin Lopatko Lindman; Bodil Weidung; Jan Olsson; Maria Josefsson; Eloise Kok; Anders Johansson; Sture Eriksson; Göran Hallmans; Fredrik Elgh; Hugo Lövheim

doi:10.1016/j.trci.2019.09.014

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

Alzheimers Dement (N Y). 2019 Nov 4:5:697-704. doi: 10.1016/j.trci.2019.09.014. eCollection 2019.

Authors

Karin Lopatko Lindman¹, Bodil Weidung^{1

2}, Jan Olsson^{3

4}, Maria Josefsson⁵, Eloise Kok⁶, Anders Johansson^{7

8}, Sture Eriksson^{1

8}, Göran Hallmans⁸, Fredrik Elgh^{3

4}, Hugo Lövheim^{1

9}

Affiliations

¹ Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umeå University, Umeå, Sweden.
² Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden.
³ Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
⁴ Section of Virology, Umeå University, Umeå, Sweden.
⁵ Centre for Demographic and Ageing Research, Umeå University, Umeå, Sweden.
⁶ Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
⁷ Department of Odontology, Umeå University, Umeå, Sweden.
⁸ Department of Public Health and Clinical Medicine, Sustainable Health, Umeå University, Umeå, Sweden.
⁹ Wallenberg Centre for molecular Medicine (WCMM), Umeå University, Umeå, Sweden.

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 APOEε4 heterozygosity (APOEε2/ε4 or ε3/ε4) 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 APOEε4 allele and other AD genetic risk factors might potentiate the risk of HSV1-associated AD.

Keywords: APOEε4; Alzheimer's disease; Apolipoprotein E4; Dementia; HSV; Herpes simplex; Nested case-control study.