Abstract
Alzheimer’s disease (AD) is a multifactorial disease with a still barely understood etiology. Herpes simplex virus 1 (HSV-1) has long been suspected to play a role in the pathogenesis of AD because of its neurotropism, high rate of infection in the general population, and life-long persistence in neuronal cells, particularly in the same brain regions that are usually altered in AD. The goal of this study was to evaluate HSV-1-specific humoral immune responses in patients with a diagnosis of either AD or amnestic mild cognitive impairment (aMCI), and to verify the possible relation between HSV-1-specific antibody (Ab) titers and cortical damage; results were compared to those obtained in a group of healthy controls (HC). HSV-1 serum IgG titers were measured in 225 subjects (83 AD, 68 aMCI, and 74 HC). HSV-specific Ab avidity and cortical gray matter volumes analyzed by magnetic resonance imaging (MRI) were evaluated as well in a subgroup of these individuals (44 AD, 23 aMCI, and 26 HC). Results showed that, whereas HSV-1 seroprevalence and IgG avidity were comparable in the three groups, increased Ab titers (p < 0.001) were detected in AD and aMCI compared to HC. Positive significant correlations were detected in AD patients alone between HSV-1 IgG titers and cortical volumes in orbitofrontal (region of interest, ROI1 RSp0.56; p = 0.0001) and bilateral temporal cortices (ROI2 RSp0.57; p < 0.0001; ROI3 RSp0.48; p = 0.001); no correlations could be detected between IgG avidity and MRI parameters. Results herein suggest that a strong HSV-1-specific humoral response could be protective toward AD-associated cortical damage.
Highlights
Alzheimer’s disease (AD) is a neurodegenerative disorder involving gray matter (GM) tissue that is considered to be part of a continuum of clinical and biological phenomena
Recent results reported an increased herpes simplex virus type 1 (HSV-1) IgG Ab avidity index in amnestic mild cognitive impairment (aMCI) patients compared to AD and healthy controls (HC) (Kobayashi et al, 2013), suggesting that viral reactivation is a frequent event in the prodromal stage of AD. Based on these previous results we investigated whether the correlation we detected between HSV-1-specific Ab titers and magnetic resonance imaging (MRI) voxel based morphometry (VBM) parameters could be observed in aMCI as well; possible associations between HSV-1 specific IgG avidity and preservation of brain areas were analyzed in a subgroup of AD and MCI patients
HSV-1 SEROPREVALENCE, TITERS, AND AVIDITY no differences were observed among the groups when HSV-1 seroprevalence was analyzed (AD = 97.6%; aMCI = 95.6%; HC = 98.6%), ANOVA comparisons showed that the three groups significantly differed with regard to HSV-1 Ab titers (p < 0.001)
Summary
Alzheimer’s disease (AD) is a neurodegenerative disorder involving gray matter (GM) tissue that is considered to be part of a continuum of clinical and biological phenomena. AD is the most common form of dementia in the elderly, affecting more than 25 million people worldwide, with a prevalence of 5% after 65 years of age, increasing to about 30% in people aged 85 years or older. The amnestic mild cognitive impairment (aMCI) is a syndrome with a high risk of progression to AD, and it could constitute a prodromal stage of this disorder and it represents the borderland condition between normal aging and AD dementia (Petersen, 2004). Over the years many environmental and genetic components have been hypothesized to be risk factors for this disease, and a viral component has long been suspected to play a critical role in the pathogenesis of AD (Honjo et al, 2009; Ball et al, 2013). A number of experimental and epidemiological data suggest that herpes simplex virus type 1 (HSV-1), a neurotropic agent that is often found in elderly brain (Jamieson et al, 1991; Wozniak et al, 2005), could have a key pathogenic role in AD (rev. in Agostini et al, 2014)
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