Reactivated herpes simplex infection increases the risk of Alzheimer's disease

Abstract

Positivity for anti-HSV IgM, a sign of reactivated infection, was found to almost double the risk for AD, whereas the presence of anti-HSV IgG antibodies did not affect the risk.

Herpes simplex infection and the risk of Alzheimer's disease: A nested case-control study

“…Hence, the current results confirm previous findings indicating a role of HSV infection in the early development of AD [4,5]. The HSV-associated risk for developing AD also appeared to be especially increased among those older than 60 years at time of plasma sampling, and among women.…”

“…The choice of cut-off in time between sampling and AD diagnosis, used to exclude those with shorter time, affected the results, however, a cut-off of anywhere between 5.5 and 9.5 years resulted in a significantly increased risk for AD associated with anti-HSV IgG positivity. Two epidemiological cohort studies investigating the risk associated with HSV for AD have previously been published [4,5]. Both found an increased risk of AD associated with the presence of anti-HSV IgM antibodies indicative of reactivated infection, but not an increased risk associated with carriage of HSV per se, as measured by presence of anti-HSV IgG antibodies.…”

“…A large proportion of the population carry HSV [5], therefore, additional factors must be considered as modifiers of the AD risk associated with HSV. An individual's humoral immune response to infection might be one such factor.…”

“…Lycke and coworkers first described an increased prevalence of anti-HSV antibodies among persons with dementia [2], and a few years later Ball presented a hypothesis involving HSV as a cause of Alzheimer's disease (AD) based on similarities between HSV encephalitis and AD [3]. Recent epidemiological cohort studies by ourselves, and others, have indeed identified an increased risk of AD following HSV reactivation, as measured by the presence of anti-HSV immunoglobulin M (IgM) antibodies [4,5]. A possible connection is further supported by studies demonstrating the detection of HSV1 within brain tissue from patients with AD and specifically within amyloid plaques [6][7][8][9][10], and by the finding that HSV1 infection can induce amyloid beta production and tau hyperphosphorylation in cultured neural cell types [11][12][13][14][15][16][17].…”

A protective role for herpes simplex virus type-1-specific humoral immunity in Alzheimer’s Disease

“…Results from two independent longitudinal studies [18,19] seem to confirm this idea. In these cohorts, the presence of HSV-specific IgM was shown to associate with a significantly increased risk of developing AD.…”