Alzheimer’s Disease, which constitutes 60% of total dementia cases1, is a neurological disorder that causes a progressive decline in brain function. It is mainly diagnosed in people over the age of 65, where it is called late-onset Alzheimer’s, but can also occur in younger demographics referred to as early-onset Alzheimer’s. Symptoms of the disease may begin as minor memory problems and having trouble concentrating but will slowly evolve into language problems, dysphagia and increasing disorientation while performing simple tasks2. Alzheimer’s Disease had an estimated prevalence of 3,690,000 in 2019 in EU5 countries3 (France, UK, Germany, Italy and Spain), however, there is currently no treatment available to halt its progression but only to alleviate its symptoms. This highlights a requirement to develop a therapeutic drug to treat the underlying condition.

The cause of the disorder is currently believed to be a consequence of an excessive accumulation of abnormal proteins-amyloid plaques and tau tangles in the brain. Amyloid fragments are natural aggregates of protein that are broken down into beta amyloid strands. Usually, these strands are small enough to dissolve and be easily excreted from the body. However, if the initial fragment is not cleaved correctly, it results in large insoluble beta amyloid strands not being expelled from the brain.  Consequently, the beta amyloid clumps together between the neurones, forming amyloid plaques. Simultaneously, when another naturally occurring protein-tau- is misfolded, it forms insoluble twisted fibres that culminate in the death of brain cells. Tau is mainly expressed in microtubules, which has a role in the transportation of nutrients between neurons. Therefore, when these microtubules collapse due to the abnormal tau protein shape, paired with the disruption of regular processes carried out by these cells, the cells end up dying. 4

Fig 1: Accumulation of amyloid plaques 5

Scientists collaborating in Germany and USA have recently identified an antibody that binds to the microglia - the immune cells located in our brain and boosts their activity. This stimulation causes the microglia to replicate more, live longer and destroy harmful materials such as amyloid plaques, potentially providing a safeguard against Alzheimer’s Disease. In mouse models, the plaques that are speculated to cause the progressive neural degeneration associated with the disorder were degraded much quicker. The focus of this research was mainly on a receptor, TREM-2 (Triggering Receptor Expressed on Myeloid cells 2), which is found on the surface of cells such as microglia. This receptor can be expressed differently in people, which may help to clarify why some individuals have higher risks of developing Alzheimer’s disease. Based on the current research in this field, the evidence suggests that different variants of the TREM-2 receptor can inactivate the microglia which blocks the excretion of amyloid plaques and tangles.6

Currently, one of the main treatments available to people with Alzheimer’s Disease are cholinesterase inhibitors which help to provide symptomatic relief by preventing the breakdown of the neurotransmitter acetylcholine and aiding communication between neurons.  Perhaps, this new research in activating the microglia through the TREM-2 receptor may be a move towards revolutionary new research into breaking down plaques and stopping the progression or even onset of the disease.

Written by Sasha-Louise Ahlawat - Healthcare analyst, Epidemiology.

References

  1. Alzheimer’s Research UK (2018) Alzheimer’s Disease: About [Online] Available at:  https://www.alzheimersresearchuk.org/about-dementia/types-of-dementia/alzheimers-disease/about/ [Accessed: 20/03/20]
  2. Dementia UK(2020) Alzheimer’s Disease [Online] Available at: https://www.dementiauk.org/understanding-dementia/types-and-symptoms/alzheimers-disease/ [Accessed: 20/03/20]
  3.  Epiomic Database (2019) Prevalence of Alzheimer’s Disease in EU5.
  4. Bright Focus Foundation (2019) Amyloid plaques and neurofibrillary tangles [Online] Available at: https://www.brightfocus.org/alzheimers-disease/infographic/amyloid-plaques-and-neurofibrillary-tangles [Accessed: 20/03/20]
  5. Haridy R (2020) ‘Novel protein suggested as core of Alzheimer’s amyloid plaques’ New Atlas
  6. Pharmanews.eu (2020) Immune Cells against Alzheimer’s [Online] Available at: https://www.pharmanews.eu/business/2255-immune-cells-against-alzheimer-s [Accessed: 20/03/20]
  7. NHS (2018) Overview: Alzheimer’s Disease [Online] Available at: https://www.nhs.uk/conditions/alzheimers-disease/ [Accessed: 20/03/20]