A genetic signature including apolipoprotein E epsilon 4 potentiates the risk of herpes simplex-associated Alzheimer's disease

IntroductionHerpes simplex virus type 1 (HSV1) in combination with genetic susceptibility has previously been implicated in Alzheimer's disease (AD) pathogenesis. MethodsPlasma from 360 AD cases, obtained on average 9.6years before diagnosis, and their age- and sex-matched controls, were analyz...

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Bibliographic Details
Published in:Alzheimer's & Dementia: Translational Research & Clinical Interventions
Main Authors: Lindman, Karin Lopatko, Weidung, Bodil, Olsson, Jan, Josefsson, Maria, Kok, Eloise, Johansson, Anders, Eriksson, Sture, Hallmans, Goran, Elgh, Fredrik, Lovheim, Hugo
Format: Article in Journal/Newspaper
Language:English
Published: Uppsala universitet, Geriatrik 2019
Subjects:
Herpes simplex
HSV
Apolipoprotein E4
APOE epsilon 4
Alzheimer's disease
Dementia
Nested case-control study
Neurology
Neurologi
Neurosciences
Neurovetenskaper
Clinical Medicine
Klinisk medicin
Iceland
Online Access:http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-477235
https://doi.org/10.1016/j.trci.2019.09.014
Description
Summary:IntroductionHerpes simplex virus type 1 (HSV1) in combination with genetic susceptibility has previously been implicated in Alzheimer's disease (AD) pathogenesis. MethodsPlasma from 360 AD cases, obtained on average 9.6years before diagnosis, and their age- and sex-matched controls, were analyzed for anti-HSV1 immunoglobulin (Ig) G with enzyme-linked immunosorbent assays (ELISAs). APOE genotype and nine other selected risk genes for AD were extracted from a genome-wide association study analysis by deCODE genetics, Reykjavik, Iceland. ResultsThe interaction between APOE epsilon 4 heterozygosity (APOE epsilon 2/epsilon 4 or epsilon 3/epsilon 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). DiscussionThe present findings suggest that the APOE epsilon 4 allele and other AD genetic risk factors might potentiate the risk of HSV1-associated AD.

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