An international group of senior scientists and clinicians has published an editorial arguing that specific microbes—a herpesvirus and certain bacteria—are major contributors to Alzheimer’s disease. Published online in the peer-reviewed Journal of Alzheimer’s Disease, the editorial calls for urgent, targeted research and, critically, for clinical trials testing antimicrobial and related treatments for Alzheimer’s.
The authors base their appeal on a substantial and growing body of published evidence linking microbes to Alzheimer’s. Their editorial collates and interprets this research, demonstrating consistent associations between particular pathogens and Alzheimer’s pathology. Despite this evidence, the infectious hypothesis has often been dismissed as controversial, and proposals to fund clinical trials targeting microbes have been rejected. This reluctance persists even though more than 400 Alzheimer’s trials based on other hypotheses failed over a recent ten-year span.
Resistance to a microbial explanation for Alzheimer’s mirrors historical scientific pushback against early findings that viruses cause certain cancers and that bacteria cause stomach ulcers—discoveries that were eventually accepted and that led to life-changing treatments. The editorial’s authors argue that a similar shift is now warranted for Alzheimer’s.
Professor Douglas B. Kell of the University of Manchester (School of Chemistry and Manchester Institute of Biotechnology), a co-author of the editorial, highlights an especially provocative finding: blood that was thought to be sterile can contain dormant microbes. This observation has implications for blood transfusion safety and for understanding how systemic infections might influence neurodegeneration.
“The evidence indicates Alzheimer’s disease includes a dormant microbial component that can be reactivated by disturbances in iron metabolism,” Professor Kell states. “If iron dysregulation wakes these microbes, then removing excess iron or otherwise modulating iron availability could slow or prevent cognitive decline. We must stop overlooking this evidence.”
Professor Resia Pretorius of the University of Pretoria, another co-author, emphasizes the link between microbial components in blood and systemic inflammation, a feature commonly observed in Alzheimer’s. She explains that bacterial cell wall components—most notably lipopolysaccharide (endotoxin)—can provoke neuroinflammation and promote formation of amyloid-β plaques, a hallmark of Alzheimer’s pathology.
The editorial also notes that microbial involvement in neurodegeneration could extend beyond Alzheimer’s, with potential implications for Parkinson’s disease and other progressive neurological disorders where inflammation and protein aggregation play central roles.
About this Alzheimer’s disease research
Source: University of Manchester
Image Credit: The image is adapted from the University of Manchester press release.
Original Research: Full open access editorial “Microbes and Alzheimer’s Disease” in Journal of Alzheimer’s Disease (published online March 8, 2016). The editorial reviews human and experimental data implicating herpes simplex virus type 1 (HSV1), Chlamydia pneumoniae, and several types of spirochetes, as well as reports of fungal infection and altered microbiota in the blood of Alzheimer’s patients.
Abstract
Microbes and Alzheimer’s Disease
We are researchers and clinicians with long-standing interests in Alzheimer’s disease (AD) and related fields. In this editorial we express concern that an infectious component of AD has been underappreciated, despite the possibility that addressing it could slow or halt disease progression. Numerous studies—predominantly in human subjects—implicate specific microbes in the elderly brain. Of particular note are herpes simplex virus type 1 (HSV1), Chlamydia pneumoniae, and various spirochetes; there are also reports of fungal organisms in Alzheimer’s brain and of abnormal blood microbiota in AD patients. The first reports of HSV1 in Alzheimer’s brain appeared nearly three decades ago, and the literature has grown steadily since then (now numbering roughly 100 studies on HSV1 alone), justifying a re-evaluation of an infection-based perspective on AD.
Alzheimer’s disease is characterized by progressive neuronal loss and synaptic dysfunction, together with accumulation of amyloid-β (Aβ) peptide—a cleavage product of amyloid-β protein precursor (AβPP)—and abnormal forms of tau protein. These neuropathological hallmarks are used diagnostically, but whether they are primary causes or downstream consequences remains unresolved. We propose that they can be understood as indicators of an infectious etiology. Microbes are capable of producing chronic as well as acute disease, and some species can remain latent for long periods before reactivating. Reactivation events—possibly decades after initial infection—may trigger neuroinflammation and the molecular cascades associated with AD. Moreover, infection does not always produce symptoms: individuals classified as controls may harbor latent pathogens without overt signs, complicating interpretation of case-control studies.
Given the accumulating evidence and the lack of convincing counter-evidence, we argue that targeted clinical trials of antimicrobial, antiviral, and related interventions should be a research priority. Such trials could determine whether reducing microbial load, blocking reactivation, modulating systemic inflammation, or correcting iron dysregulation can prevent or slow the progression of Alzheimer’s disease. The public health imperative is clear: after many unsuccessful trials based on other hypotheses, exploring the infectious hypothesis through rigorous clinical testing may open new therapeutic avenues for millions of patients and families affected by dementia.