Essential Science: Linking infections and Alzheimer’s disease

Posted Jun 13, 2016 by Tim Sandle
There are several possible causes of Alzheimer’s disease. One are being looked at by medical researchers is a possible connection between the neurodegenerative disease and certain infections.
Elderly person with his head in his hands
Elderly person with his head in his hands
Alzheimer's disease is the most common type of dementia. Dementia describes a progressive neurological disease which affects multiple brain functions, including memory. The exact causes are uncertain.
What is known about the origins of Alzheimer’s disease is the connection between the condition and a build-up of plaques of the protein amyloid beta. Amyloids are aggregates of proteins that become folded into the wrong shape, allowing many copies of that protein to stick together. The protein leads to a loss of brain tissue and the onset of Alzheimer's disease manifestations, such as cognitive decline. What is less clear is what causes the plaque (fibril-like structures) to develop.
The new connection with amyloid beta protein and infection is based on the link between the protein and the human body’s defense mechanism.
The right hand diagram is of the brain of a person suffering from Alzheimer s disease
The right hand diagram is of the brain of a person suffering from Alzheimer's disease
Research indicates that an alternative protein called LL37 is very similar to amyloid-beta. LL37 (as an antimicrobial peptide) play a role in the immune response, battling infections. Production of antimicrobial peptides and proteins is an important means of host defense in animals.
When amyloid beta was examined it was found that it has similar infection fighting properties. These proteins are not however, in normal circumstances, produced in response to an infection. That said, there could be circumstances where amyloid beta accumulates and cause tissue degeneration in response to an infection.
By carrying out tests using mice that had been genetically altered to have Alzheimer’s disease, scientist discovered that plaques of amyloid beta surrounded a site of infection when Salmonella bacteria were introduced. This effect was also shown with viral infections.
It is possible, therefore, that when particular infections occur the body overreacts and amyloid beta proteins are directed to infection sites along with LL37. This may occur if there are repeated infections with high numbers of contaminating microorganisms. Where there is too many amyloid beta proteins, the balance becomes toxic and Alzheimer’s disease begins to emerge.
This occurs more readily with older people. This is because an invasive pathogen - be it a virus, fungus or bacterium - enters the brain by passing through a membrane (the blood-brain barrier.) This barrier becomes more 'leaky' as people age. Once the pathogen crosses, the brain’s defense system activates to tackle the invader, through the production of the sticky beta amyloid proteins.
PET scans showing the differances between a normal older adult s brain and the brain of an older adu...
PET scans showing the differances between a normal older adult's brain and the brain of an older adult afflicted with Alzheimer's disease. — On photo (left to right): PET scan of normal brain, PET scan of Alzheimer’s disease brain.
National Institutes of Health
This finding caused broadcaster PBS to tweet: "Alzheimer's disease could be a late-blooming symptom of a brain infection that occurred earlier in life..." Similarly, health technology company IMS Health APAC (@IMSHealthAPAC) commented: " [#Therapy] #Alzheimer's disease may stem from toxic remnants of brain's attempt to fight off infection."
Commenting on the research, lead scientist Dr. Rudolph Tanzi said: “While our data all involve experimental models, the important next step is to search for microbes in the brains of Alzheimer’s patients that may have triggered amyloid deposition as a protective response.”
He also added: “If we can identify the culprits – be they bacteria, viruses, or yeast – we may be able to therapeutically target them for primary prevention of the disease.”
The new research was carried out at the Massachusetts General Hospital. The findings of the research are published in the journal Science Translational Medicine. The research paper is titled “Amyloid- peptide protects against microbial infection in mouse and worm models of Alzheimers disease.”
In related news, Toxoplasma gondii, a protozoan parasite may be a specific infection that has a connection with Alzheimer's disease. Research using mice has shown that the parasitic infection leads to a disruption of neurotransmitters in the brain. In turn, this appears to trigger neurological disease. Importantly, this trigger primarily affects those already predisposed to such a disease.
Scanning electron micrograph of a pair of Schistosoma mansoni
Scanning electron micrograph of a pair of Schistosoma mansoni
Davies Laboratory Uniformed Services University Bethesda, MD
T. gondii is a commonly occurring parasite, globally, infecting a third of the world's population. The reason why the parasite is linked to Alzheimer's disease is because it leads to a significant increase in glutamate, which is the major neurotransmitter in the brain (transmitting excitatory signals between neurons.)
This article is part of Digital Journal's regular Essential Science columns. Each week we explore a topical and important scientific issue. Last week we examined a lens that can produce clear magnification of nanoscale objects. Remarkably the lens was made from paint whitener on a sliver of glass. The week before we looked at the topic of sending ultrasonic signals through animals tissue in order to program medical devices.