At its most recent meeting the National Advisory Council on Aging (NACA), which advises NIH’s National Institute of Aging, took official note of the accumulated and expanding number of research reports that microbes may be playing an important role in the etiology of Alzheimer’s disease by elevating that topic to one of their “approved concepts” for research attention.
However, before the NIA can officially request research grant applications from scientists for this niche, it must first issue a Funding Opportunity Announcement, familiarly known as an “FOA”. Our impression is that the FOA is under development. When it is made public, we will include it in our “News” items.
Below is the NIA text presenting the “approved concept”.
Infectious Etiology of Alzheimer’s Disease
“The role of microbes and antimicrobial defenses in the pathogenesis of Alzheimer’s disease has been postulated and investigated for at least six decades. Since then, hundreds of reports have associated AD with diverse bacterial, fungal, and viral pathogens, most frequently implicating Herpesviridae, particularly, HSV-1, EBV, HCMV and HHV-6. These efforts have typically focused on searching the antibody repertoire of AD patients for antibodies against pathogen proteins, but the question of whether microbe-related antigens represent a causal component of AD or are opportunistic “passengers” of neurodegeneration has not been resolved.
Nevertheless, when taken in aggregate, the results of these studies are suggestive of a viral contribution to AD, though findings offer little insight into potential mechanisms, and there has been no consistent association with specific viral species. Recent molecular profiling of a large patient cohort, facilitating the integration of diverse biomedical data into a multilevel view that spans multiple disease stages, brain regions, and -omic domains, provided evidence of complex viral “activity” in the aging brain, including changes specific to AD clinical traits. Once again species of Herpesviridae were implicated. Recent efforts, unlike previous studies, point toward multiple biological mechanisms that are novel in the context of AD.
Understanding the functional roles and mechanisms of viruses in AD network biology will contribute significantly to our understanding of human clinical Alzheimer’s disease onset and progression. It will inform aspects of future translational studies in AD, including the development of “endophenotypes” of AD patients, improved molecular diagnostics, risk stratification biomarkers, and the discovery of candidate therapeutics aimed at regulating pathogen-associated networks and molecules in AD.
The initiative will:
- encourage studies to answer whether microbial pathogens in AD represent a causal component of the disease
- support studies that can leverage existing cohorts with associated samples from plasma, CSF, and brain tissue as well as imaging data to address possible links between infectious agents and clinical AD
- invite research across a broad range of topics on mechanisms underpinning neurodegeneration in AD associated with microbial pathogens in the CNS
Specifically, topics may include, but are not limited to:
- studies involving Koch’s postulates linking infectious agents and AD (i.e., pathogens must be present in every case of the disease, the pathogen must be isolated from the infected host and grown in culture, and the disease must be reproduced when the pathogen is transferred into a healthy susceptible host)
- identification of host genes and gene networks that are most commonly perturbed by pathogens in the brains of AD patients
- research on amyloidosis as a protective mechanism against microbial infection
- mechanisms linking systemic inflammation with peripheral amyloidosis
- research on mechanisms by which AD pathology may increase the vulnerability of the CNS to microbial infection.
Reprinted from: https://www.nia.nih.gov/approved-concepts#infectious