Alzheimer's disease (AD), also known as Alzheimer's, is a chronic neurodegenerative disorder with hallmark amyloid plaques in brain tissue. The diseases commences slowly and worsens over time (Sjogren et al. 1952). Although it has been investigated for over six decades, the cause of AD is still not completely understood. It was initially thought to be caused by genetic heritability (autosomal mutation leading to aggregation of β-amyloid and misfolded tau proteins) or head injury. However, hundreds of drug trials targeting the accumulation of sticky amyloid plaques and misfolded tau proteins in the brain have failed to yield any results. Although increasing evidence suggests that microbes and antimicrobial defense could play a critical role in causing AD (van den Pol 2009; Mawanda and Wallace 2013), the pathogenic microbes that contribute to AD onset and progression remain unknown.
Human herpes viruses (HHVs) are common in the brains of the elderly (Kleinschmidt-DeMasters and Gilden 2001). Although they are usually dormant, they can become active in response to stress or if the immune system is compromised. The herpes simplex virus in particular is known to damage the central nervous system and the limbic system in the brain and it has been suggested that it may cause symptoms similar to AD (Bourgade et al. 2015). However, there is no strong evidence supporting the viral hypothesis and the link with AD has been suspected for a while. In a recent study, Readhead et al. (2018) developed a multiscale-network method, which they used to establish that two other common human herpesviruses, HHV-6A and HHV-7, could be key causal contributors to AD, although HSV co-infection was also observed in some cases. This study began by comparing the specific characteristics of two distinct AD-associated phenotypes, namely, individuals with preclinical AD, who were cognitively intact at the time of death, and cognitively intact persons without neuropathology, who served as the healthy controls. They next performed functional genomic analysis and found multiple lines of evidence of preclinical AD network alterations consistent with viral activity. These observations were further confirmed by viral and cellular RNA transcriptomic analysis of samples collected from patients with late-onset AD and neuropathologically and cognitively normal controls, as well as integrating -omic domain and diverse biomedical data from large patient cohorts including different disease stages and brain regions. This study provides compelling evidence that both HHV-6A and HHV-7 are linked to neuropathology and AD development. However, many questions regarding the characterization of these two viruses remain to be investigated (Fig. 1).
Common Infections May Lead to Alzheimer's Disease
- Received Date: 27 July 2018
- Accepted Date: 24 August 2018
- Published Date: 17 September 2018
Abstract: Recent study by Joel Dudley and colleagues published in Neuron on July 11, demonstrated that both HHV-6A and HHV-7 could be key causal contributors to Alzheimer’s disease (AD). However, among various biological and technical issues, we review how complicate to demonstrate the link of HHV-6A and HHV-7 infection with AD in current situation, and highlight the potential open research directions of follow-up studies in the future.