New research has found that the body’s immune system may play a role in causing dementia. The causes of Alzheimer’s are not known, other than a few characteristic changes in the brain. This latest study provides a new piece in an incredibly important puzzle.
Background
Every year, there are over 10 million new cases of dementia across the world. It can be a truly worrying disease for the patient’s family, as your loved one gradually deteriorates and forgets who they are – losing their sense of self.
The causes of Alzheimer’s are still mostly unknown. There are certain risk factors known; including age, family history, head trauma and heart disease.
Alzheimer’s disease and dementia are often used interchangeably – to clarify, dementia is ‘a group of symptoms associated with an ongoing decline of brain functioning’, as described on the NHS website. Alzheimer’s disease is the most common cause of dementia.
The brain primarily consists of neurons. These are cells that communicate to each other to send messages throughout the brain and the body. The messages are encoded in electrical signals. To pass the electrical signals from one neuron to the next, it must be passed across the synapse – a small gap between neurons. At the synapse, one neuron converts its electrical signal into a chemical messenger (neurotransmitter) that passes across the synapse and is received by the second neuron. The second neuron then receives the neurotransmitter and converts the message into an electrical impulse. The possible causes of Alzheimer’s disrupt the communication through synapses.
One possible cause of Alzheimer’s is accumulation of proteins around neurons. Two proteins have been identified as characteristic of Alzheimer’s disease. Amyloid-beta is a protein that will bind to other amyloid beta molecules forming a larger structure. If this structure is arranged improperly, a plaque forms outside the neurons. This disrupts the function of neurons, as they cannot relay messages through electrical signals with other neurons.
The other protein involved is tau. Tau is normally found within neurons, bound to a specific cellular structure. With an abnormal chemical change, tau begins to aggregate with other tau molecules, forming structures known as tangles. Tau aggregation occurs in areas of the brain associated with memory. Furthermore, accumulation of amyloid-beta has shown correlation in causing greater accumulation of tau at a certain threshold. Brain atrophy is associated with tau deposits in neurons.
New findings
New research has looked at how tau deposits and amyloid beta accumulation affect the immune system’s activity in the brain. Support cells called microglia normally remove deposits and toxins in the brain, including amyloid beta plaques. In Alzheimer’s patients, the microglia do not properly clear the plaques. Instead, they release chemical messengers that trigger inflammation. This inflammation does more harm than good to neurons.
The harm caused by the immune response is the focus of this new research. T cells are a type of immune cell that cross from the blood to the brain in response to inflammation. The hypothesis of this study was that T cells and microglia act together to damage the brain in Alzheimer’s.
Chen and his team from the Washington University School of Medicine used mice to study this. They looked at mice with amyloid beta deposition or tau aggregation. Their data showed that in the tau mice, there were many more T cells than in the amyloid beta mice. A specific type of T cell was found in tau mice – the activated CD8+ T cell (CD8 is a marker to differentiate T cell subtypes). CD8+ T cells act to kill neurons in Alzheimer’s. However, the toxic factor that T cells release to do this is unknown.
Chen’s research also explored treatments. Tau mice were given a drug during neurodegeneration that would kill either microglia or T cells. With these drugs, brain atrophy decreased. T cells were also depleted when microglia were killed. These findings give rise to the notion of a complex interplay between microglia and T cells that act toxically on neurons.
This could be a very promising step towards an effective Alzheimer’s treatment. Therapeutic approaches to control T cell activity in the brain may help to prevent further damage in Alzheimer’s patients. More testing on animal models is needed before any human trial can begin. It could be years before any treatment arises from this, but it is a significant jump in our understanding of one of the world’s most common diseases.
