A global team of leading scientists and clinicians have come together to write an editorial suggesting that certain microbes - a specific virus and two specific types of bacteria - are the main cause of Alzheimer's disease. Their work, published online in the prestigious Journal of Alzheimer's Disease, emphasises the urgent need for further research - and, more importantly, clinical trials of antimicrobials and related agents to treat the disease.
This important call to action is based on substantial published evidence on Alzheimer's disease. The team's groundbreaking editorial summarises the abundant data implicating these microbes, but until now this work has been largely ignored or dismissed as controversial - despite the lack of evidence to the contrary. As a result, proposals to fund clinical trials have been rejected, despite the fact that over 400 unsuccessful Alzheimer's disease clinical trials based on other concepts have been conducted in the last decade.
The resistance to the microbial concepts is similar to the fierce resistance to studies a few years ago that showed that viruses cause certain types of cancer and that a bacterium causes stomach ulcers. These concepts eventually proved valid, leading to successful clinical trials and the subsequent development of appropriate treatments.
Professor Douglas Kell of the University of Manchester's School of Chemistry and the Manchester Institute of Biotechnology is one of the authors of the editorial. He says supposedly sterile red blood cells contain dormant microbes, which also has implications for blood transfusions.
"We are saying that there is incontrovertible evidence that Alzheimer's disease has a dormant microbial component, and that this can be awakened by iron dysregulation. Removing this iron will slow or prevent cognitive degeneration - we cannot continue to ignore all the evidence," said Professor Douglas Kell.
Professor Resia Pretorius of the University of Pretoria, who worked with Douglas Kell on the editorial, said, "The microbial presence in the blood may also play a fundamental role as an agent of systemic inflammation, which is a hallmark of Alzheimer's disease - particularly the bacterial cell wall component and the endotoxin, lipopolysaccharide. In addition, there is ample evidence that this can cause neuroinflammation and amyloid-β plaque formation."
The findings of this editorial may also have implications for the future treatment of Parkinson's disease and other progressive neurological disorders.
Microbes and Alzheimer's disease
We are researchers and clinicians working on Alzheimer's disease (AD) or related topics, and we write to express our concern that a particular aspect of the disease has been neglected, even though treatment based on it could slow or halt the progression of AD. We refer to the many studies, especially in humans, that implicate specific microbes in the brains of older people, particularly herpes simplex virus type 1 (HSV1), Chlamydia pneumoniae and various types of spirochetes, in the aetiology of AD. Fungal infection of the brain in AD [5, 6] has also been described, as have abnormal microbes in the blood of AD patients. The first observations of HSV1 in the brains of AD patients were reported almost three decades ago]. The ever-growing number of these studies (now about 100 on HSV1 alone) warrants a re-evaluation of the infection and AD concept.
AD is associated with neuronal loss and progressive synaptic dysfunction, accompanied by the deposition of amyloid-β (Aβ) peptide, a cleavage product of the amyloid-β protein precursor (AβPP), and abnormal forms of tau protein, markers that have been used as diagnostic criteria for the disease. These represent the markers of AD, but whether they are the cause or the consequences of AD is not known. We suspect that these are indicators of an infectious aetiology. In AD, people are often unaware that microbes can cause chronic as well as acute disease, that some microbes can remain latent in the body and have the potential to reactivate, the effects of which can occur years after initial infection, and that people can be infected but not necessarily affected, so that even if they are infected, the "controls" are asymptomatic.
"Microbes and Alzheimer's" by Itzhaki, Ruth F.; Lathe, Richard; Balin, Brian J.; Ball, Melvyn J.; Träger, Elaine L.; Bullido, Maria J.Carter, Chris; Clerici, Mario; Cosby, S. Louise; Field, Hugh; Fulop, Tamas; Grassi, Claudio; Griffin, W. Sue T.; Haas, Jürgen; Hudson, Alan P.; Kamer, Angela R.; Kell, Douglas B.Licastro, Federico; Letenneur, Luc; Lövheim, Hugo; Mancuso, Roberta; Miklossy, Judith; Lagunas, Carola Otth; Palamara, Anna Teresa; Perry, George; Preston, Christopher; Pretorius, Etheresia; Strandberg, Timo; Tabet, Naji; Taylor-Robinson, Simon D.; and Whittum-Hudson, Judith A. in Journal of Alzheimer's Disease. Published online 8 March 2016 doi:10.3233/JAD-160152