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Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer's Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post-mortem brain versus cerebrospinal fluid (CSF), blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, PCR and sequencing techniques, and bioinformatic tools will be evaluated, in addition to direct microbial culture and metabolomic techniques. The goal is to provide a roadmap for detecting infectious agents in patients with mild cognitive impairment or AD. Positive findings would then prompt tailoring of antimicrobial treatments that might attenuate or remit mounting clinical deficits in a subset of patients.

Recent commentary in Neurotherapeutics by Nath critically addresses the earlier report by Tzeng et al. that aggressive antiviral treatment (AVT) against herpes simplex virus (HSV) was associated with a later decrease in the incidence of Alzheimer’s disease (AD). Nath raises issues that we respond to: we point out that (i) the treated group (probably with severe infection) is likely to harbor genetic risk alleles that predispose to both AD and HSV infection—the potential treatment bias cited by Nath would support (rather than challenge) the preventive effect of AVT; (ii) HSV is well known to establish persistent infection in the brain; and (iii) current AVT compounds used to combat herpes viruses are highly specific for this class of viruses. Instead of “alternative fact,” the findings of Tzeng et al. argue in favor of clinical trials of AVT in AD. Electronic supplementary material The online version of this article (10.1007/s13311-018-00700-5) contains supplementary material, which is available to authorized users.

Various infectious agents, and viruses in particular, have been proposed as potential causes of Alzheimer's disease. Herpes simplex virus type 1 (HSV-1) is one of the stronger candidates because it is neurotropic, ubiquitous in the general population and able to establish lifelong latency in the host. The body of evidence for the role of HSV-1 in Alzheimer's disease is contentious but centres around its presence in the regions of the brain affected by Alzheimer's disease. The fact that HSV-1 is also present in elderly patients without the disease suggests that the virus is not an independent cause of the condition. The incidence of Alzheimer's disease is highest in carriers of the apolipoprotein (APO) E-e4 allele who harbour HSV-1 DNA in the CNS, so it is possible that these agents are co-factors for the disease. However, studies investigating this have been small and limited by the need to access brain tissue from non-diseased APOE-e4 carriers. Human herpesvirus type 6 (HHV-6) is another virus investigated as a potential contributor to Alzheimer's disease. However, it is uncertain whether its presence is a cause or a consequence of the disease and it may be that HHV-6 merely exacerbates the potentially harmful effects of HSV-1 in APOE-e4 carriers. It is difficult to ascertain the role of an infectious agent in Alzheimer's disease due to the difficulty of establishing the timepoint at which the agent becomes involved. Further research into the possible link between herpesviruses and Alzheimer's disease is therefore required.

Molecular and cell biology of neuropsychiatric diseases , Molecular and cell biology of neuropsychiatric diseases , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی